3qte

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Crystal structure of human alpha-defensin 6 (H27W mutant)

Structural highlights

3qte is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.949Å
Ligands:CL, GOL
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DEF6_HUMAN Has very low antimicrobial activity against Gram-negative and Gram-positive bacteria. May protect cells against infection with HIV-1.[1] [2]

Publication Abstract from PubMed

Defensins are antimicrobial peptides that contribute broadly to innate immunity, including protection of mucosal tissues. Human alpha-defensin (HD) 6 is highly expressed by secretory Paneth cells of the small intestine. However, in contrast to the other defensins, it lacks appreciable bactericidal activity. Nevertheless, we report here that HD6 affords protection against invasion by enteric bacterial pathogens in vitro and in vivo. After stochastic binding to bacterial surface proteins, HD6 undergoes ordered self-assembly to form fibrils and nanonets that surround and entangle bacteria. This self-assembly mechanism occurs in vivo, requires histidine-27, and is consistent with x-ray crystallography data. These findings support a key role for HD6 in protecting the small intestine against invasion by diverse enteric pathogens and may explain the conservation of HD6 throughout Hominidae evolution.

Human alpha-defensin 6 promotes mucosal innate immunity through self-assembled peptide nanonets.,Chu H, Pazgier M, Jung G, Nuccio SP, Castillo PA, de Jong MF, Winter MG, Winter SE, Wehkamp J, Shen B, Salzman NH, Underwood MA, Tsolis RM, Young GM, Lu W, Lehrer RI, Baumler AJ, Bevins CL Science. 2012 Jul 27;337(6093):477-81. Epub 2012 Jun 21. PMID:22722251[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
92 reviews cite this structure
Microbiota-mediated colonization resistance against intestinal pathogens.
Buffie et al. (2013)
91 more
119 other articles
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See Also

References

  1. ↑ Ericksen B, Wu Z, Lu W, Lehrer RI. Antibacterial activity and specificity of the six human {alpha}-defensins. Antimicrob Agents Chemother. 2005 Jan;49(1):269-75. PMID:15616305 doi:10.1128/AAC.49.1.269-275.2005
  2. ↑ Szyk A, Wu Z, Tucker K, Yang D, Lu W, Lubkowski J. Crystal structures of human alpha-defensins HNP4, HD5, and HD6. Protein Sci. 2006 Dec;15(12):2749-60. Epub 2006 Nov 6. PMID:17088326 doi:ps.062336606
  3. ↑ Chu H, Pazgier M, Jung G, Nuccio SP, Castillo PA, de Jong MF, Winter MG, Winter SE, Wehkamp J, Shen B, Salzman NH, Underwood MA, Tsolis RM, Young GM, Lu W, Lehrer RI, Baumler AJ, Bevins CL. Human alpha-defensin 6 promotes mucosal innate immunity through self-assembled peptide nanonets. Science. 2012 Jul 27;337(6093):477-81. Epub 2012 Jun 21. PMID:22722251 doi:http://dx.doi.org/10.1126/science.1218831

Contents


PDB ID 3qte

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OCA

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