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Antibody WN1 222-5 Mimics Toll-like Receptor 4 Binding in the Recognition of LPS

Di Padova, Franco E. and Gomery, Kathryn and Evans, Stephen V (2012) Antibody WN1 222-5 Mimics Toll-like Receptor 4 Binding in the Recognition of LPS. Proocedings national academy sciences, 109 (51). pp. 20877-20882.

Abstract

Escherichia coli infections, a leading cause of septic shock, remain a major threat to human health due to the fatal action to endotoxin (lipopolysaccharide, LPS). 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 (TLR4) to induce immune cell activation. The 1.73 Å 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 TLR4, 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 sepsis therapy independent of lipid A antagonists.

Item Type: Article
Date Deposited: 02 May 2016 23:45
Last Modified: 02 May 2016 23:45
URI: https://oak.novartis.com/id/eprint/9023

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