Beta-defensin 2 (BD-2) also known as skin-antimicrobial peptide 1 (SAP1) is a peptide that in humans is encoded by the DEFB4 (defensin, beta 4) gene.[3]
hBD-2 is a protein whose primary structure is made by 64 aminoacids. At concentrations ≤2.4 mM, hBD-2 is monomeric.[4] The structure is amphiphilic with a nonuniform surface distribution of positive charge and contains several key structural elements, including a triple-stranded, antiparallel beta sheet with strands 2 and 3 in a beta hairpin conformation. The determination of other structural elements depends on the technique used. When X-ray crystallography is used an alpha helix can be observed at the N-terminal end of the protein (PDB codes: 1fd3,1fd4, and 6cs9). When using NMR this alpha-helix does not appear (PDB code: 1e4q), however this structure was determined using a truncated version of hBD-2 which was missing the initial 4 amino acids, and may be the reason for the discrepancy.
Function
Defensins form a family of microbicidal and cytotoxic peptides made by neutrophils. Members of the defensin family are highly similar in protein sequence. Beta-defensin 2 is an antibiotic peptide which is locally regulated by inflammation.[5]
Human beta-defensin 2 is produced by a number of epithelial cells and exhibits potent antimicrobial activity against Gram-negative bacteria and Candida, but not Gram-positive S. aureus. It has been speculated that beta-defensin 2 may contribute to the infrequency of Gram-negative infections on skin and lung tissue.[6]
hBD-2 represents the first human defensin that is produced following stimulation of epithelial cells by contact with microorganisms such as P. aeruginosa or cytokines such as TNF-alpha and IL-1 beta. The HBD-2 gene and protein are locally expressed in keratinocytes associated with inflammatory skin lesions. It is intriguing to speculate that HBD-2 is a dynamic component of the local epithelial defense system of the skin and respiratory tract having a role to protect surfaces from infection, and providing a possible reason why skin and lung infections with Gram-negative bacteria are rather rare.[6]
Although this protein doesn’t have any antibacterial activity against Gram-positive bacteria, there is a study showing that there is a synergy between hBD-2 and other proteins.[7] One example of this synergistic effect is with epiP, a protein segregated by some strains of S. epidermidis. hBD2, holding hands with epiP, is capable of killing S. aureus, a Gram-positive bacteria responsible of human diseases.
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Harder J, Bartels J, Christophers E, Schröder JM (June 1997). "A peptide antibiotic from human skin". Nature. 387 (6636): 861. doi:10.1038/43088. PMID 9202117. S2CID 4354862.
^Sawai MV, Jia HP, Liu L, Aseyev V, Wiencek JM, McCray PB, Ganz T, Kearney WR, Tack BF (April 2001). "The NMR structure of human beta-defensin-2 reveals a novel alpha-helical segment". Biochemistry. 40 (13): 3810–3816. doi:10.1021/bi002519d. PMID 11300761.
^ abSchröder JM, Harder J (June 1999). "Human beta-defensin-2". The International Journal of Biochemistry & Cell Biology. 31 (6): 645–651. doi:10.1016/S1357-2725(99)00013-8. PMID 10404637.
^Iwase T, Uehara Y, Shinji H, Tajima A, Seo H, Takada K, Agata T, Mizunoe Y (May 2010). "Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization". Nature. 465 (7296): 346–349. Bibcode:2010Natur.465..346I. doi:10.1038/nature09074. PMID 20485435. S2CID 4392908.
External links
Human DEFB4A genome location and DEFB4A gene details page in the UCSC Genome Browser.
Further reading
Weinberg A, Krisanaprakornkit S, Dale BA (1999). "Epithelial antimicrobial peptides: review and significance for oral applications". Critical Reviews in Oral Biology and Medicine. 9 (4): 399–414. doi:10.1177/10454411980090040201. PMID 9825219.
Schröder JM, Harder J (June 1999). "Human beta-defensin-2". The International Journal of Biochemistry & Cell Biology. 31 (6): 645–651. doi:10.1016/S1357-2725(99)00013-8. PMID 10404637.
Bals R, Wang X, Wu Z, Freeman T, Bafna V, Zasloff M, Wilson JM (September 1998). "Human beta-defensin 2 is a salt-sensitive peptide antibiotic expressed in human lung". The Journal of Clinical Investigation. 102 (5): 874–880. doi:10.1172/JCI2410. PMC508952. PMID 9727055.
Liu L, Wang L, Jia HP, Zhao C, Heng HH, Schutte BC, McCray PB, Ganz T (November 1998). "Structure and mapping of the human beta-defensin HBD-2 gene and its expression at sites of inflammation". Gene. 222 (2): 237–244. doi:10.1016/S0378-1119(98)00480-6. PMID 9831658.
Mathews M, Jia HP, Guthmiller JM, Losh G, Graham S, Johnson GK, Tack BF, McCray PB (June 1999). "Production of beta-defensin antimicrobial peptides by the oral mucosa and salivary glands". Infection and Immunity. 67 (6): 2740–2745. doi:10.1128/IAI.67.6.2740-2745.1999. PMC96577. PMID 10338476.
Jia HP, Mills JN, Barahmand-Pour F, Nishimura D, Mallampali RK, Wang G, Wiles K, Tack BF, Bevins CL, McCray PB (September 1999). "Molecular cloning and characterization of rat genes encoding homologues of human beta-defensins". Infection and Immunity. 67 (9): 4827–4833. doi:10.1128/IAI.67.9.4827-4833.1999. PMC96815. PMID 10456937.
Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J, Anderson M, Schröder JM, Wang JM, Howard OM, Oppenheim JJ (October 1999). "Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6". Science. 286 (5439): 525–528. doi:10.1126/science.286.5439.525. PMID 10521347.
Diamond G, Kaiser V, Rhodes J, Russell JP, Bevins CL (January 2000). "Transcriptional regulation of beta-defensin gene expression in tracheal epithelial cells". Infection and Immunity. 68 (1): 113–119. doi:10.1128/iai.68.1.113-119.2000. PMC97109. PMID 10603376.
Harder J, Meyer-Hoffert U, Teran LM, Schwichtenberg L, Bartels J, Maune S, Schröder JM (June 2000). "Mucoid Pseudomonas aeruginosa, TNF-alpha, and IL-1beta, but not IL-6, induce human beta-defensin-2 in respiratory epithelia". American Journal of Respiratory Cell and Molecular Biology. 22 (6): 714–721. doi:10.1165/ajrcmb.22.6.4023. PMID 10837369.
Hoover DM, Rajashankar KR, Blumenthal R, Puri A, Oppenheim JJ, Chertov O, Lubkowski J (October 2000). "The structure of human beta-defensin-2 shows evidence of higher order oligomerization". The Journal of Biological Chemistry. 275 (42): 32911–32918. doi:10.1074/jbc.M006098200. PMID 10906336.
Meyer JE, Harder J, Görögh T, Schröder JM, Maune S (July 2000). "[hBD-2 gene expression in nasal mucosa]". Laryngo- Rhino- Otologie. 79 (7): 400–403. doi:10.1055/s-2000-4626. PMID 11005092.
Ali RS, Falconer A, Ikram M, Bissett CE, Cerio R, Quinn AG (July 2001). "Expression of the peptide antibiotics human beta defensin-1 and human beta defensin-2 in normal human skin". The Journal of Investigative Dermatology. 117 (1): 106–111. doi:10.1046/j.0022-202x.2001.01401.x. PMID 11442756.
Carothers DG, Graham SM, Jia HP, Ackermann MR, Tack BF, McCray PB (2001). "Production of beta-defensin antimicrobial peptides by maxillary sinus mucosa". American Journal of Rhinology. 15 (3): 175–179. doi:10.2500/105065801779954238. PMID 11453504. S2CID 31583849.
Biragyn A, Surenhu M, Yang D, Ruffini PA, Haines BA, Klyushnenkova E, Oppenheim JJ, Kwak LW (December 2001). "Mediators of innate immunity that target immature, but not mature, dendritic cells induce antitumor immunity when genetically fused with nonimmunogenic tumor antigens". Journal of Immunology. 167 (11): 6644–6653. doi:10.4049/jimmunol.167.11.6644. PMID 11714836.
Bauer F, Schweimer K, Klüver E, Conejo-Garcia JR, Forssmann WG, Rösch P, Adermann K, Sticht H (December 2001). "Structure determination of human and murine beta-defensins reveals structural conservation in the absence of significant sequence similarity". Protein Science. 10 (12): 2470–2479. doi:10.1110/ps.24401. PMC2374044. PMID 11714914.
Takahashi A, Wada A, Ogushi K, Maeda K, Kawahara T, Mawatari K, Kurazono H, Moss J, Hirayama T, Nakaya Y (November 2001). "Production of beta-defensin-2 by human colonic epithelial cells induced by Salmonella enteritidis flagella filament structural protein". FEBS Letters. 508 (3): 484–488. doi:10.1016/S0014-5793(01)03088-5. PMID 11728477. S2CID 24925463.
Schibli DJ, Hunter HN, Aseyev V, Starner TD, Wiencek JM, McCray PB, Tack BF, Vogel HJ (March 2002). "The solution structures of the human beta-defensins lead to a better understanding of the potent bactericidal activity of HBD3 against Staphylococcus aureus". The Journal of Biological Chemistry. 277 (10): 8279–8289. doi:10.1074/jbc.M108830200. PMID 11741980.
February 06, 2023
beta, defensin, also, known, skin, antimicrobial, peptide, sap1, peptide, that, humans, encoded, defb4, defensin, beta, gene, defb4bavailable, structurespdbhuman, uniprot, search, pdbe, rcsblist, codes1e4q, 1fd3, 1fd4, 1fqqidentifiersaliasesdefb4b, defb4p, def. Beta defensin 2 BD 2 also known as skin antimicrobial peptide 1 SAP1 is a peptide that in humans is encoded by the DEFB4 defensin beta 4 gene 3 DEFB4BAvailable structuresPDBHuman UniProt search PDBe RCSBList of PDB id codes1E4Q 1FD3 1FD4 1FQQIdentifiersAliasesDEFB4B DEFB4P defensin beta 4BExternal IDsHomoloGene 122147 GeneCards DEFB4BGene location Human Chr Chromosome 8 human 1 Band8p23 1Start7 414 855 bp 1 End7 416 863 bp 1 RNA expression patternBgeeHumanMouse ortholog Top expressed ingastric mucosathymusmuscle tissueislet of Langerhanscellurinary bladdermonocytebloodendometriumvaginan aMore reference expression dataBioGPSn aGene ontologyMolecular functionprotein binding CCR6 chemokine receptor binding chemoattractant activityCellular componentGolgi lumen extracellular region extracellular space intracellular anatomical structureBiological processG protein coupled receptor signaling pathway defense response immune response chemotaxis defense response to Gram negative bacterium defense response to bacterium defense response to Gram positive bacterium antimicrobial humoral response antimicrobial humoral immune response mediated by antimicrobial peptide positive chemotaxis cell chemotaxisSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez100289462n aEnsemblENSG00000177257ENSG00000275444ENSG00000285433n aUniProtO15263n aRefSeq mRNA NM 001205266n aRefSeq protein NP 001192195NP 004933n aLocation UCSC Chr 8 7 41 7 42 Mbn aPubMed search 2 n aWikidataView Edit HumanHuman beta defensin 2 hBD 2 is a cysteine rich cationic low molecular weight antimicrobial peptide recently discovered in lesional skin Contents 1 Structure 2 Function 3 References 4 External links 5 Further readingStructure EdithBD 2 is a protein whose primary structure is made by 64 aminoacids At concentrations 2 4 mM hBD 2 is monomeric 4 The structure is amphiphilic with a nonuniform surface distribution of positive charge and contains several key structural elements including a triple stranded antiparallel beta sheet with strands 2 and 3 in a beta hairpin conformation The determination of other structural elements depends on the technique used When X ray crystallography is used an alpha helix can be observed at the N terminal end of the protein PDB codes 1fd3 1fd4 and 6cs9 When using NMR this alpha helix does not appear PDB code 1e4q however this structure was determined using a truncated version of hBD 2 which was missing the initial 4 amino acids and may be the reason for the discrepancy Function EditDefensins form a family of microbicidal and cytotoxic peptides made by neutrophils Members of the defensin family are highly similar in protein sequence Beta defensin 2 is an antibiotic peptide which is locally regulated by inflammation 5 Human beta defensin 2 is produced by a number of epithelial cells and exhibits potent antimicrobial activity against Gram negative bacteria and Candida but not Gram positive S aureus It has been speculated that beta defensin 2 may contribute to the infrequency of Gram negative infections on skin and lung tissue 6 hBD 2 represents the first human defensin that is produced following stimulation of epithelial cells by contact with microorganisms such as P aeruginosa or cytokines such as TNF alpha and IL 1 beta The HBD 2 gene and protein are locally expressed in keratinocytes associated with inflammatory skin lesions It is intriguing to speculate that HBD 2 is a dynamic component of the local epithelial defense system of the skin and respiratory tract having a role to protect surfaces from infection and providing a possible reason why skin and lung infections with Gram negative bacteria are rather rare 6 Although this protein doesn t have any antibacterial activity against Gram positive bacteria there is a study showing that there is a synergy between hBD 2 and other proteins 7 One example of this synergistic effect is with epiP a protein segregated by some strains of S epidermidis hBD2 holding hands with epiP is capable of killing S aureus a Gram positive bacteria responsible of human diseases References Edit a b c ENSG00000275444 ENSG00000285433 GRCh38 Ensembl release 89 ENSG00000177257 ENSG00000275444 ENSG00000285433 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Harder J Bartels J Christophers E Schroder JM June 1997 A peptide antibiotic from human skin Nature 387 6636 861 doi 10 1038 43088 PMID 9202117 S2CID 4354862 Sawai MV Jia HP Liu L Aseyev V Wiencek JM McCray PB Ganz T Kearney WR Tack BF April 2001 The NMR structure of human beta defensin 2 reveals a novel alpha helical segment Biochemistry 40 13 3810 3816 doi 10 1021 bi002519d PMID 11300761 Entrez Gene DEFB4 defensin beta 4 a b Schroder JM Harder J June 1999 Human beta defensin 2 The International Journal of Biochemistry amp Cell Biology 31 6 645 651 doi 10 1016 S1357 2725 99 00013 8 PMID 10404637 Iwase T Uehara Y Shinji H Tajima A Seo H Takada K Agata T Mizunoe Y May 2010 Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization Nature 465 7296 346 349 Bibcode 2010Natur 465 346I doi 10 1038 nature09074 PMID 20485435 S2CID 4392908 External links EditHuman DEFB4A genome location and DEFB4A gene details page in the UCSC Genome Browser Further reading EditWeinberg A Krisanaprakornkit S Dale BA 1999 Epithelial antimicrobial peptides review and significance for oral applications Critical Reviews in Oral Biology and Medicine 9 4 399 414 doi 10 1177 10454411980090040201 PMID 9825219 Schroder JM Harder J June 1999 Human beta defensin 2 The International Journal of Biochemistry amp Cell Biology 31 6 645 651 doi 10 1016 S1357 2725 99 00013 8 PMID 10404637 Bals R Wang X Wu Z Freeman T Bafna V Zasloff M Wilson JM September 1998 Human beta defensin 2 is a salt sensitive peptide antibiotic expressed in human lung The Journal of Clinical Investigation 102 5 874 880 doi 10 1172 JCI2410 PMC 508952 PMID 9727055 Liu L Wang L Jia HP Zhao C Heng HH Schutte BC McCray PB Ganz T November 1998 Structure and mapping of the human beta defensin HBD 2 gene and its expression at sites of inflammation Gene 222 2 237 244 doi 10 1016 S0378 1119 98 00480 6 PMID 9831658 Mathews M Jia HP Guthmiller JM Losh G Graham S Johnson GK Tack BF McCray PB June 1999 Production of beta defensin antimicrobial peptides by the oral mucosa and salivary glands Infection and Immunity 67 6 2740 2745 doi 10 1128 IAI 67 6 2740 2745 1999 PMC 96577 PMID 10338476 Jia HP Mills JN Barahmand Pour F Nishimura D Mallampali RK Wang G Wiles K Tack BF Bevins CL McCray PB September 1999 Molecular cloning and characterization of rat genes encoding homologues of human beta defensins Infection and Immunity 67 9 4827 4833 doi 10 1128 IAI 67 9 4827 4833 1999 PMC 96815 PMID 10456937 Yang D Chertov O Bykovskaia SN Chen Q Buffo MJ Shogan J Anderson M Schroder JM Wang JM Howard OM Oppenheim JJ October 1999 Beta defensins linking innate and adaptive immunity through dendritic and T cell CCR6 Science 286 5439 525 528 doi 10 1126 science 286 5439 525 PMID 10521347 Diamond G Kaiser V Rhodes J Russell JP Bevins CL January 2000 Transcriptional regulation of beta defensin gene expression in tracheal epithelial cells Infection and Immunity 68 1 113 119 doi 10 1128 iai 68 1 113 119 2000 PMC 97109 PMID 10603376 Harder J Meyer Hoffert U Teran LM Schwichtenberg L Bartels J Maune S Schroder JM June 2000 Mucoid Pseudomonas aeruginosa TNF alpha and IL 1beta but not IL 6 induce human beta defensin 2 in respiratory epithelia American Journal of Respiratory Cell and Molecular Biology 22 6 714 721 doi 10 1165 ajrcmb 22 6 4023 PMID 10837369 Hoover DM Rajashankar KR Blumenthal R Puri A Oppenheim JJ Chertov O Lubkowski J October 2000 The structure of human beta defensin 2 shows evidence of higher order oligomerization The Journal of Biological Chemistry 275 42 32911 32918 doi 10 1074 jbc M006098200 PMID 10906336 Meyer JE Harder J Gorogh T Schroder JM Maune S July 2000 hBD 2 gene expression in nasal mucosa Laryngo Rhino Otologie 79 7 400 403 doi 10 1055 s 2000 4626 PMID 11005092 Ali RS Falconer A Ikram M Bissett CE Cerio R Quinn AG July 2001 Expression of the peptide antibiotics human beta defensin 1 and human beta defensin 2 in normal human skin The Journal of Investigative Dermatology 117 1 106 111 doi 10 1046 j 0022 202x 2001 01401 x PMID 11442756 Carothers DG Graham SM Jia HP Ackermann MR Tack BF McCray PB 2001 Production of beta defensin antimicrobial peptides by maxillary sinus mucosa American Journal of Rhinology 15 3 175 179 doi 10 2500 105065801779954238 PMID 11453504 S2CID 31583849 Biragyn A Surenhu M Yang D Ruffini PA Haines BA Klyushnenkova E Oppenheim JJ Kwak LW December 2001 Mediators of innate immunity that target immature but not mature dendritic cells induce antitumor immunity when genetically fused with nonimmunogenic tumor antigens Journal of Immunology 167 11 6644 6653 doi 10 4049 jimmunol 167 11 6644 PMID 11714836 Bauer F Schweimer K Kluver E Conejo Garcia JR Forssmann WG Rosch P Adermann K Sticht H December 2001 Structure determination of human and murine beta defensins reveals structural conservation in the absence of significant sequence similarity Protein Science 10 12 2470 2479 doi 10 1110 ps 24401 PMC 2374044 PMID 11714914 Takahashi A Wada A Ogushi K Maeda K Kawahara T Mawatari K Kurazono H Moss J Hirayama T Nakaya Y November 2001 Production of beta defensin 2 by human colonic epithelial cells induced by Salmonella enteritidis flagella filament structural protein FEBS Letters 508 3 484 488 doi 10 1016 S0014 5793 01 03088 5 PMID 11728477 S2CID 24925463 Schibli DJ Hunter HN Aseyev V Starner TD Wiencek JM McCray PB Tack BF Vogel HJ March 2002 The solution structures of the human beta defensins lead to a better understanding of the potent bactericidal activity of HBD3 against Staphylococcus aureus The Journal of Biological Chemistry 277 10 8279 8289 doi 10 1074 jbc M108830200 PMID 11741980 Retrieved 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