Abstract:
: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-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 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.
journal_name
Proc Natl Acad Sci U S Aauthors
Gomery K,Müller-Loennies S,Brooks CL,Brade L,Kosma P,Di Padova F,Brade H,Evans SVdoi
10.1073/pnas.1209253109subject
Has Abstractpub_date
2012-12-18 00:00:00pages
20877-82issue
51eissn
0027-8424issn
1091-6490pii
1209253109journal_volume
109pub_type
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