Definition
Complementarity-determining regions (CDRs) are hypervariable loop structures in the antigen-binding parts of antibodies and determine the specificity of antigen binding1. Improvement of antibody affinity may be obtained by site-directed mutagenesis of individual amino acid residues in the antibody CDRs1. CDR-H3/C2 is a peptide derived from the third heavy chain domain and modified by cyclization. It is capable of neutralizing HIV-1 replication1.
Discovery
CDR-H3/C2 was constructed in 1993 using sequences of mouse monoclonal antibody F58 that has the capacity to neutralize HIV-11.
Classification
CDR-H3/C2 belongs to the immunoglobulin superfamily of peptides1.
Structural Characteristics
CDR-H3/C2 is a 16 amino acid peptide with the sequence- CDLIYYDYEEDYYFDC, the ends of which are held by a disulphide bond to form a cyclic structure1.
Mode of action
CDR-H3/C2 binds effectively to HIV-1 variable region V3 and most likely preventing the interaction of HIV-1 to antibodies on the host cell1. This in turn inhibits infection of HIV into the host cell1.
Functions
CDR-H3/C2 is a neutralizing peptide for HIV-11.
References
1.Levi M, Sällberg M, Rudén U, Herlyn D, Maruyama H, Wigzell H, Marks J, Wahren B (1993). A complementarity-determining region synthetic peptide acts as a miniantibody and neutralizes human immunodeficiency virus type 1 in vitro. Proc Natl Acad Sci, 90(10), 4374-8.
Thursday, July 2, 2009
Delta-Sleep Inducing Peptide (DSIP) and Analogs
Definition
Delta sleep-inducing peptide (DSIP) is an endogenous neuropeptide that crosses the blood-brain barrier. It is associated with natural sleep and enhanced ectroencephalogram (EEG) delta rhythm.
Discovery
DSIP was isolated from the extracorporeal dislysate of cerebral venous blood in rabbits which was subjected to hypnogenic electrical stimulation1.
Classification.
The analogs of DSIP are synthesized by modification of the primary sequence of the nanopeptide. Phosphorylated DSIP, DSIP (1-4), DSIP (1-8), DSIP (2-8), DSIP (2-9), DSIP (5-9) etc are some of the analogs of DSIP.
Structural Characteristics
The primary amino acid sequence of DSIP is Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu with molecular weight of 848.8 kDa.
Mode of action
The action of DSIP is mediated by the activation of the serotoninergic system of the brain. It increases the activity of monoamine oxidase type A in mitochondria, the substrate of this enzyme is serotonin2.
Functions
DSIP has several physiological effects in addition to its ability to promote sleep in animals. It is also involved in neuroendocrine regulation and release of anterior pituitary hormones. In rodents and humans, DSIP influence in the secretion of adrenocorticotropic hormone (ACTH), luteinizing hormone (LH) and growth hormone (GH) 3,4,5,6. It also plays a role in the regulation of the circadian rhythms7.
References
1.Schoenenberger GA, Monnier M (1977). Characterization of a delta-electroencephalogram (-sleep)-inducing peptide. Proc Natl Acad Sci USA, 74, 1282-1286.
2.Shandra AA, Godlevskii LS, Brusentsov AI, Petrashevich VP, Vast'yanov RS, Nikel B, Mikhaleva II (1998). Delta-sleep-inducing peptide and its analogs and the serotoninergic system in the development of anticonvulsive influences. Neurosci Behav Physiol., 28(5), 521-526.
3.Sahu A, Klara SP (1987). Delta sleep inducing peptide (DSIP) stimulates LH releasein steroid-primed ovariectomized rats. Life Sci, 12, 1201-1206.
4.Okajima T, Hertting G (1986). Delta-sleep inducing peptide (DSIP) inhibited CRF-induced ACTH secretion from rat anterior pituitary gland in vitro. Horm Metab Res., 18, 497-499.
5.Iyer KS, McCann SM (1987) Delta sleep inducing peptide (DSIP) stimulates growthhormone (GH) release in the rat by hypothalamic and pituitary actions. Peptides, 8, 45-48
6.Chiodera P, Volpi R, Caapretti L, Giacalone G, Caffari G, Davoli C, Nigro E,Coiro V (1994) Different effects of delta-sleep-inducing peptide on arginine-vasopressin and ACTH secretion in normal men. Horm Res., 42, 267-272
7.S. Inoue, M. Kimura-Takeuchi, V. M. Koval'zon,V. N. Kalikhevich, and S. I. Churkina(1994). Effects of Some DSIP Peptide Analogs on Rat Sleep for Intraventricular Infusion. Bulletin of Experimental Biology and Medicine., 117, 58.
Delta sleep-inducing peptide (DSIP) is an endogenous neuropeptide that crosses the blood-brain barrier. It is associated with natural sleep and enhanced ectroencephalogram (EEG) delta rhythm.
Discovery
DSIP was isolated from the extracorporeal dislysate of cerebral venous blood in rabbits which was subjected to hypnogenic electrical stimulation1.
Classification.
The analogs of DSIP are synthesized by modification of the primary sequence of the nanopeptide. Phosphorylated DSIP, DSIP (1-4), DSIP (1-8), DSIP (2-8), DSIP (2-9), DSIP (5-9) etc are some of the analogs of DSIP.
Structural Characteristics
The primary amino acid sequence of DSIP is Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu with molecular weight of 848.8 kDa.
Mode of action
The action of DSIP is mediated by the activation of the serotoninergic system of the brain. It increases the activity of monoamine oxidase type A in mitochondria, the substrate of this enzyme is serotonin2.
Functions
DSIP has several physiological effects in addition to its ability to promote sleep in animals. It is also involved in neuroendocrine regulation and release of anterior pituitary hormones. In rodents and humans, DSIP influence in the secretion of adrenocorticotropic hormone (ACTH), luteinizing hormone (LH) and growth hormone (GH) 3,4,5,6. It also plays a role in the regulation of the circadian rhythms7.
References
1.Schoenenberger GA, Monnier M (1977). Characterization of a delta-electroencephalogram (-sleep)-inducing peptide. Proc Natl Acad Sci USA, 74, 1282-1286.
2.Shandra AA, Godlevskii LS, Brusentsov AI, Petrashevich VP, Vast'yanov RS, Nikel B, Mikhaleva II (1998). Delta-sleep-inducing peptide and its analogs and the serotoninergic system in the development of anticonvulsive influences. Neurosci Behav Physiol., 28(5), 521-526.
3.Sahu A, Klara SP (1987). Delta sleep inducing peptide (DSIP) stimulates LH releasein steroid-primed ovariectomized rats. Life Sci, 12, 1201-1206.
4.Okajima T, Hertting G (1986). Delta-sleep inducing peptide (DSIP) inhibited CRF-induced ACTH secretion from rat anterior pituitary gland in vitro. Horm Metab Res., 18, 497-499.
5.Iyer KS, McCann SM (1987) Delta sleep inducing peptide (DSIP) stimulates growthhormone (GH) release in the rat by hypothalamic and pituitary actions. Peptides, 8, 45-48
6.Chiodera P, Volpi R, Caapretti L, Giacalone G, Caffari G, Davoli C, Nigro E,Coiro V (1994) Different effects of delta-sleep-inducing peptide on arginine-vasopressin and ACTH secretion in normal men. Horm Res., 42, 267-272
7.S. Inoue, M. Kimura-Takeuchi, V. M. Koval'zon,V. N. Kalikhevich, and S. I. Churkina(1994). Effects of Some DSIP Peptide Analogs on Rat Sleep for Intraventricular Infusion. Bulletin of Experimental Biology and Medicine., 117, 58.
CDK5 (Cyclin-dependent Kinase 5)
Definition
Cyclin dependent kinase 5 (CDK5) is a unique member of cyclin dependent kinase family members that is not activated by a cyclin1. Instead it is activated by a kinase, p35. Unlike other CDKs, it plays a major role in cell cell communication, cell morphology and motility1.
Discovery
CDK5 originally named nclk1 was first identified in 1992 in a cDNA library screen of an adult rat brain using mouse cdk1 as a probe2.
Classification
CDK5 belongs to the highly conserved family of Ser/Thr protein kinases2.
Structural Characteristics
CDK5 consists of two lobes, a small N-terminal lobe that binds to cyclin and a large lobe at the C terminus that binds to the substrate3. The ATP binding domain is located in the cleft between the two lobes3. Ser159 in CDK5 is known to be important for its interaction with p353.
Mode of action
CDK5 is abundant in post mitotic neurons4. CDK5 first binds to its regulatory proteins p35/p25/p39 which then triggers its phosphorylation and activation4. Activated CDK5 phosphorylates several proteins in the cell to exert its functions4. The activity of CDK5 is regulated by p35 4.
Functions
CDK5 is important in several aspects of neuronal development3. It is implicated in cytoskeleton assembly and organization during axonal growth, neuronal differentiation and migration, synaptic activities in mature neurons and cell death in neurodegenerative diseases4. CDK5 is also involved in the regulation of exo and endocytosis of synaptic vesicles4. It modulates signal transduction pathways regulating neuronal survival4. CDK5 is implicated in Alzheimer’s disease as it is involved in the hyperphosphorylation of the protein Tau that leads to neuronal cell death5.
References
1.Meyerson M, Enders GH, Wu CL, Su LK, Gorka C, Nelson C, Harlow E, Tsai LH (1992). A family of human cdc2-related protein kinases. Embo J. 11 (8), 2909–17.
2.Hellmich MR, Pant HC, Wada E, Battey JF (1992). Neuronal cdc2-like kinase: a cdc2-related protein kinase with predominantly neuronal expression. Proc Natl Acad Sci, 89(22), 10867-71.
3.Book: Cyclin Dependent Kinase 5 (CDK5), edited by Nancy Y and Tsai LH, 191-211.
4.Maccioni RB, Otth C, Concha II, Muñoz JP (2001). The protein kinase Cdk5. Structural aspects, roles in neurogenesis and involvement in Alzheimer's pathology. Eur J Biochem, 268(6), 1518-27.
5.Dhariwala FA, Rajadhyaksha MS (2008). An unusual member of the Cdk family: Cdk5. Cell Mol Neurobiol, 28(3), 351-69.
Cyclin dependent kinase 5 (CDK5) is a unique member of cyclin dependent kinase family members that is not activated by a cyclin1. Instead it is activated by a kinase, p35. Unlike other CDKs, it plays a major role in cell cell communication, cell morphology and motility1.
Discovery
CDK5 originally named nclk1 was first identified in 1992 in a cDNA library screen of an adult rat brain using mouse cdk1 as a probe2.
Classification
CDK5 belongs to the highly conserved family of Ser/Thr protein kinases2.
Structural Characteristics
CDK5 consists of two lobes, a small N-terminal lobe that binds to cyclin and a large lobe at the C terminus that binds to the substrate3. The ATP binding domain is located in the cleft between the two lobes3. Ser159 in CDK5 is known to be important for its interaction with p353.
Mode of action
CDK5 is abundant in post mitotic neurons4. CDK5 first binds to its regulatory proteins p35/p25/p39 which then triggers its phosphorylation and activation4. Activated CDK5 phosphorylates several proteins in the cell to exert its functions4. The activity of CDK5 is regulated by p35 4.
Functions
CDK5 is important in several aspects of neuronal development3. It is implicated in cytoskeleton assembly and organization during axonal growth, neuronal differentiation and migration, synaptic activities in mature neurons and cell death in neurodegenerative diseases4. CDK5 is also involved in the regulation of exo and endocytosis of synaptic vesicles4. It modulates signal transduction pathways regulating neuronal survival4. CDK5 is implicated in Alzheimer’s disease as it is involved in the hyperphosphorylation of the protein Tau that leads to neuronal cell death5.
References
1.Meyerson M, Enders GH, Wu CL, Su LK, Gorka C, Nelson C, Harlow E, Tsai LH (1992). A family of human cdc2-related protein kinases. Embo J. 11 (8), 2909–17.
2.Hellmich MR, Pant HC, Wada E, Battey JF (1992). Neuronal cdc2-like kinase: a cdc2-related protein kinase with predominantly neuronal expression. Proc Natl Acad Sci, 89(22), 10867-71.
3.Book: Cyclin Dependent Kinase 5 (CDK5), edited by Nancy Y and Tsai LH, 191-211.
4.Maccioni RB, Otth C, Concha II, Muñoz JP (2001). The protein kinase Cdk5. Structural aspects, roles in neurogenesis and involvement in Alzheimer's pathology. Eur J Biochem, 268(6), 1518-27.
5.Dhariwala FA, Rajadhyaksha MS (2008). An unusual member of the Cdk family: Cdk5. Cell Mol Neurobiol, 28(3), 351-69.
CDK5 (Cyclin-dependent Kinase 5)
Definition
Cyclin dependent kinase 5 (CDK5) is a unique member of cyclin dependent kinase family members that is not activated by a cyclin1. Instead it is activated by a kinase, p35. Unlike other CDKs, it plays a major role in cell cell communication, cell morphology and motility1.
Discovery
CDK5 originally named nclk1 was first identified in 1992 in a cDNA library screen of an adult rat brain using mouse cdk1 as a probe2.
Classification
CDK5 belongs to the highly conserved family of Ser/Thr protein kinases2.
Structural Characteristics
CDK5 consists of two lobes, a small N-terminal lobe that binds to cyclin and a large lobe at the C terminus that binds to the substrate3. The ATP binding domain is located in the cleft between the two lobes3. Ser159 in CDK5 is known to be important for its interaction with p353.
Mode of action
CDK5 is abundant in post mitotic neurons4. CDK5 first binds to its regulatory proteins p35/p25/p39 which then triggers its phosphorylation and activation4. Activated CDK5 phosphorylates several proteins in the cell to exert its functions4. The activity of CDK5 is regulated by p35 4.
Functions
CDK5 is important in several aspects of neuronal development3. It is implicated in cytoskeleton assembly and organization during axonal growth, neuronal differentiation and migration, synaptic activities in mature neurons and cell death in neurodegenerative diseases4. CDK5 is also involved in the regulation of exo and endocytosis of synaptic vesicles4. It modulates signal transduction pathways regulating neuronal survival4. CDK5 is implicated in Alzheimer’s disease as it is involved in the hyperphosphorylation of the protein Tau that leads to neuronal cell death5.
References
1.Meyerson M, Enders GH, Wu CL, Su LK, Gorka C, Nelson C, Harlow E, Tsai LH (1992). A family of human cdc2-related protein kinases. Embo J. 11 (8), 2909–17.
2.Hellmich MR, Pant HC, Wada E, Battey JF (1992). Neuronal cdc2-like kinase: a cdc2-related protein kinase with predominantly neuronal expression. Proc Natl Acad Sci, 89(22), 10867-71.
3.Book: Cyclin Dependent Kinase 5 (CDK5), edited by Nancy Y and Tsai LH, 191-211.
4.Maccioni RB, Otth C, Concha II, Muñoz JP (2001). The protein kinase Cdk5. Structural aspects, roles in neurogenesis and involvement in Alzheimer's pathology. Eur J Biochem, 268(6), 1518-27.
5.Dhariwala FA, Rajadhyaksha MS (2008). An unusual member of the Cdk family: Cdk5. Cell Mol Neurobiol, 28(3), 351-69.
Cyclin dependent kinase 5 (CDK5) is a unique member of cyclin dependent kinase family members that is not activated by a cyclin1. Instead it is activated by a kinase, p35. Unlike other CDKs, it plays a major role in cell cell communication, cell morphology and motility1.
Discovery
CDK5 originally named nclk1 was first identified in 1992 in a cDNA library screen of an adult rat brain using mouse cdk1 as a probe2.
Classification
CDK5 belongs to the highly conserved family of Ser/Thr protein kinases2.
Structural Characteristics
CDK5 consists of two lobes, a small N-terminal lobe that binds to cyclin and a large lobe at the C terminus that binds to the substrate3. The ATP binding domain is located in the cleft between the two lobes3. Ser159 in CDK5 is known to be important for its interaction with p353.
Mode of action
CDK5 is abundant in post mitotic neurons4. CDK5 first binds to its regulatory proteins p35/p25/p39 which then triggers its phosphorylation and activation4. Activated CDK5 phosphorylates several proteins in the cell to exert its functions4. The activity of CDK5 is regulated by p35 4.
Functions
CDK5 is important in several aspects of neuronal development3. It is implicated in cytoskeleton assembly and organization during axonal growth, neuronal differentiation and migration, synaptic activities in mature neurons and cell death in neurodegenerative diseases4. CDK5 is also involved in the regulation of exo and endocytosis of synaptic vesicles4. It modulates signal transduction pathways regulating neuronal survival4. CDK5 is implicated in Alzheimer’s disease as it is involved in the hyperphosphorylation of the protein Tau that leads to neuronal cell death5.
References
1.Meyerson M, Enders GH, Wu CL, Su LK, Gorka C, Nelson C, Harlow E, Tsai LH (1992). A family of human cdc2-related protein kinases. Embo J. 11 (8), 2909–17.
2.Hellmich MR, Pant HC, Wada E, Battey JF (1992). Neuronal cdc2-like kinase: a cdc2-related protein kinase with predominantly neuronal expression. Proc Natl Acad Sci, 89(22), 10867-71.
3.Book: Cyclin Dependent Kinase 5 (CDK5), edited by Nancy Y and Tsai LH, 191-211.
4.Maccioni RB, Otth C, Concha II, Muñoz JP (2001). The protein kinase Cdk5. Structural aspects, roles in neurogenesis and involvement in Alzheimer's pathology. Eur J Biochem, 268(6), 1518-27.
5.Dhariwala FA, Rajadhyaksha MS (2008). An unusual member of the Cdk family: Cdk5. Cell Mol Neurobiol, 28(3), 351-69.
CD4 Peptide Fragments
Definition
CD4 is a glycoprotein expressed on T cells, monocytes, macrophages and dendritic cells1. CD4 peptides are peptides derived from CD4 sequence that are used mainly to study its functions1.
Discovery
CD4 was first identified in peripheral lymphocytes by genomic blotting techniques in 19862.
Classification
CD4 is a glycoprotein that belongs to the immunoglobulin superfamily of proteins2.
Structural Characteristics
CD4 has four immunoglobulin domains (D1 to D4) that are exposed on the extracellular surface of the cell: D1 and D3 resemble immunoglobulin variable (IgV) domains3. D2 and D4 resemble immunoglobulin constant (IgC) domains3. CD4 uses its D1 domain to interact with the ß2-domain of MHC class II molecules3. The short cytoplasmic/intracellular tail (C) of CD4 contains a special sequence of amino acids that allow it to interact with the lck molecule described above3.
Mode of action
CD4+ T cells are initially activated when an antigen presenting cells presents an antigen bound to MHC molecule4. CD4 bound to MHC in turn activates several kinases that allow the activation of CD4 and CD3 through phosphorylation4. Activated CD4 and other molecules trigger several signals in the cytosol that form the first step in T cell activation4.
Functions
CD4 is a co-receptor that assists the T cell receptor to activate its T cell following an interaction with an antigen presenting cell5. Using its portion that resides inside the T cell, CD4 amplifies the signal generated by the TCR by recruiting an enzyme, known as the tyrosine kinase lck, which is essential for activating many molecules involved in the signaling cascade of an activated T cell. CD4 also interacts directly with MHC class II molecules on the surface of the antigen presenting cell using its extracellular domain5.
CD4 is a primary receptor used by HIV-1 to gain entry into host T cells. HIV-1 attaches to CD4 with a protein in its viral envelope known as gp120 allowing HIV-1 to bind to two other surface receptors on the host cells, CCR5 or CXCR46. Following a structural change in another viral protein (gp41), HIV inserts a fusion peptide into the host cell that allows the outer membrane of the virus to fuse with the cell membrane. HIV infection leads to a progressive reduction in the number of T cells possessing CD4 receptors6.
References
1.Zhou L, Chong MM, Littman DR (2009). Plasticity of CD4+ T cell lineage differentiation. Immunity, 30(5), 646-55.
2.Isobe M, Huebner K, Maddont PJ, Littmant DL, Axelt R and Croce CM (1986). The gene encoding the T-cell surface protein T4 is located on human chromosome 12 (T4 glycoprotein/chromosome mapping/acquired immunodeficiency syndrome receptor/in situ hybridization/T lymphocytes. Proc. Natl. Acad. Sci. USA, 83, 4399-4402.
3.Ryu SE, Truneh A, Sweet RW, Hendrickson WA (1994). Structures of an HIV and MHC binding fragment from human CD4 as refined in two crystal lattices. Structure, 2 (1): 59–74.
4.Miceli MC, Parnes JR (1993). Role of CD4 and CD8 in T cell activation and differentiation. Adv. Immunol., 53: 59–122.
5.Harrington, LE; RD Hatton & PR Mangan (2005). Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nature Immunology, 6 (11), 1023-32.
6.Anderson JL, Hope TJ (2005). HIV accessory proteins and surviving the host cell. Current HIV/AIDS reports, 1 (1), 47–53.
CD4 is a glycoprotein expressed on T cells, monocytes, macrophages and dendritic cells1. CD4 peptides are peptides derived from CD4 sequence that are used mainly to study its functions1.
Discovery
CD4 was first identified in peripheral lymphocytes by genomic blotting techniques in 19862.
Classification
CD4 is a glycoprotein that belongs to the immunoglobulin superfamily of proteins2.
Structural Characteristics
CD4 has four immunoglobulin domains (D1 to D4) that are exposed on the extracellular surface of the cell: D1 and D3 resemble immunoglobulin variable (IgV) domains3. D2 and D4 resemble immunoglobulin constant (IgC) domains3. CD4 uses its D1 domain to interact with the ß2-domain of MHC class II molecules3. The short cytoplasmic/intracellular tail (C) of CD4 contains a special sequence of amino acids that allow it to interact with the lck molecule described above3.
Mode of action
CD4+ T cells are initially activated when an antigen presenting cells presents an antigen bound to MHC molecule4. CD4 bound to MHC in turn activates several kinases that allow the activation of CD4 and CD3 through phosphorylation4. Activated CD4 and other molecules trigger several signals in the cytosol that form the first step in T cell activation4.
Functions
CD4 is a co-receptor that assists the T cell receptor to activate its T cell following an interaction with an antigen presenting cell5. Using its portion that resides inside the T cell, CD4 amplifies the signal generated by the TCR by recruiting an enzyme, known as the tyrosine kinase lck, which is essential for activating many molecules involved in the signaling cascade of an activated T cell. CD4 also interacts directly with MHC class II molecules on the surface of the antigen presenting cell using its extracellular domain5.
CD4 is a primary receptor used by HIV-1 to gain entry into host T cells. HIV-1 attaches to CD4 with a protein in its viral envelope known as gp120 allowing HIV-1 to bind to two other surface receptors on the host cells, CCR5 or CXCR46. Following a structural change in another viral protein (gp41), HIV inserts a fusion peptide into the host cell that allows the outer membrane of the virus to fuse with the cell membrane. HIV infection leads to a progressive reduction in the number of T cells possessing CD4 receptors6.
References
1.Zhou L, Chong MM, Littman DR (2009). Plasticity of CD4+ T cell lineage differentiation. Immunity, 30(5), 646-55.
2.Isobe M, Huebner K, Maddont PJ, Littmant DL, Axelt R and Croce CM (1986). The gene encoding the T-cell surface protein T4 is located on human chromosome 12 (T4 glycoprotein/chromosome mapping/acquired immunodeficiency syndrome receptor/in situ hybridization/T lymphocytes. Proc. Natl. Acad. Sci. USA, 83, 4399-4402.
3.Ryu SE, Truneh A, Sweet RW, Hendrickson WA (1994). Structures of an HIV and MHC binding fragment from human CD4 as refined in two crystal lattices. Structure, 2 (1): 59–74.
4.Miceli MC, Parnes JR (1993). Role of CD4 and CD8 in T cell activation and differentiation. Adv. Immunol., 53: 59–122.
5.Harrington, LE; RD Hatton & PR Mangan (2005). Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nature Immunology, 6 (11), 1023-32.
6.Anderson JL, Hope TJ (2005). HIV accessory proteins and surviving the host cell. Current HIV/AIDS reports, 1 (1), 47–53.
Defensins
Definition
Defensins are small antimicrobial peptide (AMP) with a broad spectrum of antibacterial activity. It plays an important role in host defenses against infections, inflammation, wound repair and acquired immunity
Discovery
Defensins were discovered when the antimicrobial activity of rabbit and guinea-pig leukocyte lysates were studied in the 1960’s. The so-called arginine- rich cationic peptides were defined by their high cathodal electrophorectic activity mobility and attracted attention because of their isolation and detailed chemical characterization1.
Classification
The mammalian defensins can be subdivided into three main classes according to their structural differences: the a-defensins, b-defensins and q-defensins. a-Defensins have broad antimicrobial activity against Gram-negative and Gram-positive bacteria, fungi, and enveloped viruses. b-Defensins are mainly active against Gram-negative bacteria and yeast. q-Defensin is a cyclic peptide containing 18 amino acids with three disulfides discovered in macaque leukocytes2. Three defensins (human neutrophil peptide defensin [HNP]-1, HNP-2, and HNP-3) constitute between 30-50% of the total protein in azurophil granules of human polymorphonuclear neutrophils (PMN)3.
Structural Characteristics
Defensins are small cysteine-rich cationic proteins with 18-45 amino acids and with a molecular weight of 3.4 to 4.5 kDa. All defensins share a characteristic three disulfide bond motif. These cysteine disulfide bonds are essential for the biological activities of defensins.
Mode of action
The specific mechanism of antimicrobial activity involves permeabilization of bacterial membranes. It has been postulated that individual monomers oligomerize to form a pore through anionic membranes, although the evidence is only indirect4.
The microbicidal activity of defensins is brought about by permeabilization of anionic lipid bilayers and the subsequent release of cellular contents. Interactions between defensins and bacterial membranes are governed mainly by electrostatic forces. One mechanism of permeabilization is thought to involve the formation of ion pores in bacterial membranes. The second model also known as carpet model assumes that the defensins are thought to aggregate into positively charged patches that neutralize anionic lipid head groups of the membrane over a wide area around the peptides. This neutralization disrupts the integrity of the lipid bilayer, causing transient gaps to arise and allowing ions to permeate the membrane4.
Functions
Defensins are antimicrobial peptides produced by immune cells in response to bacterial infection. It also functions in blocking of human host cell invasion against HIV5 and the induction of cell-mediated immune responses against tumors in mice6. Various defensins have chemotactic activity for monocytes, T cells and dendritic cells. Defensins produced by cells in the course of innate host defense serve as signals which initiate, mobilize, and amplify adaptive immune host defenses.
References
1.Ganz.T (2003). Defensins: Antimicrobial peptides of innate immunity. Nature, 3,710-720.
2.Schneider JJ, Unholzer A, Schaller M, Schäfer-Korting M, Korting HC (2005). Human defensins. J Mol Med, 83(8), 587-595.
3.R I Lehrer, A Barton, K A Daher, S S Harwig, T Ganz, and M E Selsted (1989). Interaction of human defensins with Escherichia coli. Mechanism of bactericidal activity. J Clin Invest, 84(2), 553–561.
4.Hoover DM, Rajashankar KR, Blumenthal R, Puri A, Oppenheim JJ, Chertov O, Lubkowski J (2000). The structure of human beta-defensin-2 shows evidence of higher order oligomerization. J Biol Chem, 275(42), 32911-32918.
5.Zhang L, Yu W, He T, Yu J, Caffrey RE, Dalmasso EA, Fu S, Pham T, Mei J, Ho JJ, Zhang W, Lopez P, Ho DD (2002). Contribution of human alpha-defensin 1, 2, and 3 to the anti-HIV-1 activity of CD8 antiviral factor. Science, 303 (5657), 467.
6.Biragyn A, Ruffini PA, Leifer CA, Klyushnenkova E, Shakhov A, Chertov O, Shirakawa AK, Farber JM, Segal DM, Oppenheim JJ, Kwak LW. Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2. Science, 298(5595), 1025-1029.
Defensins are small antimicrobial peptide (AMP) with a broad spectrum of antibacterial activity. It plays an important role in host defenses against infections, inflammation, wound repair and acquired immunity
Discovery
Defensins were discovered when the antimicrobial activity of rabbit and guinea-pig leukocyte lysates were studied in the 1960’s. The so-called arginine- rich cationic peptides were defined by their high cathodal electrophorectic activity mobility and attracted attention because of their isolation and detailed chemical characterization1.
Classification
The mammalian defensins can be subdivided into three main classes according to their structural differences: the a-defensins, b-defensins and q-defensins. a-Defensins have broad antimicrobial activity against Gram-negative and Gram-positive bacteria, fungi, and enveloped viruses. b-Defensins are mainly active against Gram-negative bacteria and yeast. q-Defensin is a cyclic peptide containing 18 amino acids with three disulfides discovered in macaque leukocytes2. Three defensins (human neutrophil peptide defensin [HNP]-1, HNP-2, and HNP-3) constitute between 30-50% of the total protein in azurophil granules of human polymorphonuclear neutrophils (PMN)3.
Structural Characteristics
Defensins are small cysteine-rich cationic proteins with 18-45 amino acids and with a molecular weight of 3.4 to 4.5 kDa. All defensins share a characteristic three disulfide bond motif. These cysteine disulfide bonds are essential for the biological activities of defensins.
Mode of action
The specific mechanism of antimicrobial activity involves permeabilization of bacterial membranes. It has been postulated that individual monomers oligomerize to form a pore through anionic membranes, although the evidence is only indirect4.
The microbicidal activity of defensins is brought about by permeabilization of anionic lipid bilayers and the subsequent release of cellular contents. Interactions between defensins and bacterial membranes are governed mainly by electrostatic forces. One mechanism of permeabilization is thought to involve the formation of ion pores in bacterial membranes. The second model also known as carpet model assumes that the defensins are thought to aggregate into positively charged patches that neutralize anionic lipid head groups of the membrane over a wide area around the peptides. This neutralization disrupts the integrity of the lipid bilayer, causing transient gaps to arise and allowing ions to permeate the membrane4.
Functions
Defensins are antimicrobial peptides produced by immune cells in response to bacterial infection. It also functions in blocking of human host cell invasion against HIV5 and the induction of cell-mediated immune responses against tumors in mice6. Various defensins have chemotactic activity for monocytes, T cells and dendritic cells. Defensins produced by cells in the course of innate host defense serve as signals which initiate, mobilize, and amplify adaptive immune host defenses.
References
1.Ganz.T (2003). Defensins: Antimicrobial peptides of innate immunity. Nature, 3,710-720.
2.Schneider JJ, Unholzer A, Schaller M, Schäfer-Korting M, Korting HC (2005). Human defensins. J Mol Med, 83(8), 587-595.
3.R I Lehrer, A Barton, K A Daher, S S Harwig, T Ganz, and M E Selsted (1989). Interaction of human defensins with Escherichia coli. Mechanism of bactericidal activity. J Clin Invest, 84(2), 553–561.
4.Hoover DM, Rajashankar KR, Blumenthal R, Puri A, Oppenheim JJ, Chertov O, Lubkowski J (2000). The structure of human beta-defensin-2 shows evidence of higher order oligomerization. J Biol Chem, 275(42), 32911-32918.
5.Zhang L, Yu W, He T, Yu J, Caffrey RE, Dalmasso EA, Fu S, Pham T, Mei J, Ho JJ, Zhang W, Lopez P, Ho DD (2002). Contribution of human alpha-defensin 1, 2, and 3 to the anti-HIV-1 activity of CD8 antiviral factor. Science, 303 (5657), 467.
6.Biragyn A, Ruffini PA, Leifer CA, Klyushnenkova E, Shakhov A, Chertov O, Shirakawa AK, Farber JM, Segal DM, Oppenheim JJ, Kwak LW. Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2. Science, 298(5595), 1025-1029.
Caspase Related Peptides
Definition
Cathelin-related antimicrobial peptide (CRAMP) is a family of polypeptides found in lysosomes in polymorphonuclear leukocytes (PMNs)1. They are components of innate immunity and effectively inhibit the growth of gram-negative bacteria1.
Discovery
Cathelin was first identified in pig leukocytes as a cysteine protease inhibitor2. Since then several CRAMPs with antimicrobial activity have been identified in various animals including mouse femoral marrow cells3.
Classification
CRAMPs, members of cathelicidin gene family are antimicrobial peptides that are closely related to the cathepsin family of cysteine protease inhibitors3. Over 20 members of CRAMPs have been identified.
Structural Characteristics
CRAMPs contain a highly conserved cathelin like N terminal domain and a variable antibacterial C terminal domain3.
Mode of action
Cells producing CRAMPs such as neutrophils, monocytes and macrophages are recruited at the site of bacterial infection or wound4. CRAMPs are activated by cleavage of their N terminal cathelin domains that releases their antimicrobial domain4. Once activated, it is suggested that they may neutralize lipopolysaccharide that is present on the membrane of gram-negative bacteria thus killing them4.
Functions
CRAMPs are players in host defense mechanism against microbial attacks3. They are effective antibiotics against gram-negative bacteria4. They play an important role in blocking the onset of inflammation4. They also play a role in wound repair4. It has been suggested that they may have therapeutic potential for gram-negative bacterial sepsis and septic shock4.
References
1.Ha JM, Shin SY and Kang SW (1999). Synthesis and Antibiotic Activities of CRAMP, a Cathelin-related Antimicrobial Peptide and Its Fragments. Antibiotic Activity of CRAMP and Its Fragments Bull. Korean Chem. Soc., 20 (9) 1073.
2.Ritonja A, Kopitar M, Jerala R and Turk V (1989). Primary structure of a new cysteine proteinase inhibitor from pig leucocytes. FEBS Lett. 255, 211–214.
3.Gallo RL, Kim KJ, Bernfield M, Kozak CA, Zanetti M , Merluzzi L, and Gennaro R (1997). Identification of CRAMP, a Cathelin-related Antimicrobial Peptide Expressed in the Embryonic and Adult Mouse. J Biol. Chem., 273 (20), 13088-93.
4.Nagaoka I, Hirota S, Niyonsaba F, Hirata M, Adachi Y, Tamura H, Heumann D (2001). Cathelicidin family of antibacterial peptides CAP18 and CAP11 inhibit the expression of TNF-alpha by blocking the binding of LPS to CD14(+) cells. J Immunol., 167(6), 3329-38.
Cathelin-related antimicrobial peptide (CRAMP) is a family of polypeptides found in lysosomes in polymorphonuclear leukocytes (PMNs)1. They are components of innate immunity and effectively inhibit the growth of gram-negative bacteria1.
Discovery
Cathelin was first identified in pig leukocytes as a cysteine protease inhibitor2. Since then several CRAMPs with antimicrobial activity have been identified in various animals including mouse femoral marrow cells3.
Classification
CRAMPs, members of cathelicidin gene family are antimicrobial peptides that are closely related to the cathepsin family of cysteine protease inhibitors3. Over 20 members of CRAMPs have been identified.
Structural Characteristics
CRAMPs contain a highly conserved cathelin like N terminal domain and a variable antibacterial C terminal domain3.
Mode of action
Cells producing CRAMPs such as neutrophils, monocytes and macrophages are recruited at the site of bacterial infection or wound4. CRAMPs are activated by cleavage of their N terminal cathelin domains that releases their antimicrobial domain4. Once activated, it is suggested that they may neutralize lipopolysaccharide that is present on the membrane of gram-negative bacteria thus killing them4.
Functions
CRAMPs are players in host defense mechanism against microbial attacks3. They are effective antibiotics against gram-negative bacteria4. They play an important role in blocking the onset of inflammation4. They also play a role in wound repair4. It has been suggested that they may have therapeutic potential for gram-negative bacterial sepsis and septic shock4.
References
1.Ha JM, Shin SY and Kang SW (1999). Synthesis and Antibiotic Activities of CRAMP, a Cathelin-related Antimicrobial Peptide and Its Fragments. Antibiotic Activity of CRAMP and Its Fragments Bull. Korean Chem. Soc., 20 (9) 1073.
2.Ritonja A, Kopitar M, Jerala R and Turk V (1989). Primary structure of a new cysteine proteinase inhibitor from pig leucocytes. FEBS Lett. 255, 211–214.
3.Gallo RL, Kim KJ, Bernfield M, Kozak CA, Zanetti M , Merluzzi L, and Gennaro R (1997). Identification of CRAMP, a Cathelin-related Antimicrobial Peptide Expressed in the Embryonic and Adult Mouse. J Biol. Chem., 273 (20), 13088-93.
4.Nagaoka I, Hirota S, Niyonsaba F, Hirata M, Adachi Y, Tamura H, Heumann D (2001). Cathelicidin family of antibacterial peptides CAP18 and CAP11 inhibit the expression of TNF-alpha by blocking the binding of LPS to CD14(+) cells. J Immunol., 167(6), 3329-38.
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