Antibody WN1 222-5 mimics Toll-like receptor 4 binding in the recognition of LPS

作者：Gomery Kathryn; Mueller Loennies Sven; Brooks Cory L; Brade Lore; Kosma Paul; Di Padova Franco; Brade Helmut; Evans Stephen V

来源：Proceedings of the National Academy of Sciences, 2012, 109(51): 20877-20882.

DOI：10.1073/pnas.1209253109

Escherichia 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-angstrom 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.

• 出版日期2012-12-18