5CUI

Crystal structure of Human Defensin-5 R28A mutant.

Summary for 5CUI

• Entry DOI: 10.2210/pdb5cui/pdb
• Related: 1ZMP 5CUJ 5CUM
• Descriptor: Defensin-5, CHLORIDE ION, 2-(2-METHOXYETHOXY)ETHANOL, ... (6 entities in total)
• Functional Keywords: paneth cells defensin, human alpha-defensin, intestinal defensin, antimicrobial protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 6
• Total formula weight: 22512.04

Authors

Tolbert, W.D.,Gohain, N.,Pazgier, M. (deposition date: 2015-07-24, release date: 2016-07-27, Last modification date: 2024-10-23)

Primary citation

Xu, D.,Liao, C.,Zhang, B.,Tolbert, W.D.,He, W.,Dai, Z.,Zhang, W.,Yuan, W.,Pazgier, M.,Liu, J.,Yu, J.,Sansonetti, P.J.,Bevins, C.L.,Shao, Y.,Lu, W.
Human Enteric alpha-Defensin 5 Promotes Shigella Infection by Enhancing Bacterial Adhesion and Invasion.
Immunity, 2018

PubMed Abstract: 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 α-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.

PubMed: 29858013
DOI: 10.1016/j.immuni.2018.04.014

Experimental method

X-RAY DIFFRACTION (2.403 Å)