3v0w
From Proteopedia
Crystal structure of Fab WN1 222-5 in complex with LPS
Structural highlights
Publication Abstract from PubMedEscherichia coli infections, a leading cause of septic shock, remain a major threat to human health because of the fatal action to endotoxin (LPS). Therapeutic attempts to neutralize endotoxin currently focus on inhibiting the interaction of the toxic component lipid A with myeloid differentiating factor 2, which forms a trimeric complex together with Toll-like receptor 4 to induce immune cell activation. The 1.73-A resolution structure of the unique endotoxin-neutralizing protective antibody WN1 222-5 in complex with the core region shows that it recognizes LPS of all E. coli serovars in a manner similar to Toll-like receptor 4, revealing that protection can be achieved by targeting the inner core of LPS and that recognition of lipid A is not required. Such interference with Toll-like receptor complex formation opens new paths for antibody sepsis therapy independent of lipid A antagonists. Antibody WN1 222-5 mimics Toll-like receptor 4 binding in the recognition of LPS.,Gomery K, Muller-Loennies S, Brooks CL, Brade L, Kosma P, Di Padova F, Brade H, Evans SV Proc Natl Acad Sci U S A. 2012 Dec 18;109(51):20877-82. doi:, 10.1073/pnas.1209253109. Epub 2012 Nov 26. PMID:23184990[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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