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5cuj

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Crystal structure of Human Defensin-5 Y27A mutant crystal form 2.

Structural highlights

5cuj is a 6 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 2.08Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DEF5_HUMAN Has antimicrobial activity against Gram-negative and Gram-positive bacteria. Defensins are thought to kill microbes by permeabilizing their plasma membrane. All DEFA5 peptides exert antimicrobial activities, but their potency is affected by peptide processing.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Shigella is a Gram-negative bacterium that causes bacillary dysentery worldwide. It invades the intestinal epithelium to elicit intense inflammation and tissue damage, yet the underlying mechanisms of its host selectivity and low infectious inoculum remain perplexing. Here, we report that Shigella co-opts human alpha-defensin 5 (HD5), a host defense peptide important for intestinal homeostasis and innate immunity, to enhance its adhesion to and invasion of mucosal tissues. HD5 promoted Shigella infection in vitro in a structure-dependent manner. Shigella, commonly devoid of an effective host-adhesion apparatus, preferentially targeted HD5 to augment its ability to colonize the intestinal epithelium through interactions with multiple bacterial membrane proteins. HD5 exacerbated infectivity and Shigella-induced pathology in a culture of human colorectal tissues and three animal models. Our findings illuminate how Shigella exploits innate immunity by turning HD5 into a virulence factor for infection, unveiling a mechanism of action for this highly proficient human pathogen.

Human Enteric alpha-Defensin 5 Promotes Shigella Infection by Enhancing Bacterial Adhesion and Invasion.,Xu D, Liao C, Zhang B, Tolbert WD, He W, Dai Z, Zhang W, Yuan W, Pazgier M, Liu J, Yu J, Sansonetti PJ, Bevins CL, Shao Y, Lu W Immunity. 2018 May 22. pii: S1074-7613(18)30183-3. doi:, 10.1016/j.immuni.2018.04.014. PMID:29858013^[4]

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

References

↑ Ghosh D, Porter E, Shen B, Lee SK, Wilk D, Drazba J, Yadav SP, Crabb JW, Ganz T, Bevins CL. Paneth cell trypsin is the processing enzyme for human defensin-5. Nat Immunol. 2002 Jun;3(6):583-90. Epub 2002 May 20. PMID:12021776 doi:10.1038/ni797
↑ 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
↑ 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
↑ Xu D, Liao C, Zhang B, Tolbert WD, He W, Dai Z, Zhang W, Yuan W, Pazgier M, Liu J, Yu J, Sansonetti PJ, Bevins CL, Shao Y, Lu W. Human Enteric alpha-Defensin 5 Promotes Shigella Infection by Enhancing Bacterial Adhesion and Invasion. Immunity. 2018 May 22. pii: S1074-7613(18)30183-3. doi:, 10.1016/j.immuni.2018.04.014. PMID:29858013 doi:http://dx.doi.org/10.1016/j.immuni.2018.04.014