3V0W

Crystal structure of Fab WN1 222-5 in complex with LPS

Summary for 3V0W

• Entry DOI: 10.2210/pdb3v0w/pdb
• Descriptor: WN1 222-5 Fab (IgG2a) light chain, WN1 222-5 Fab (IgG2a) heavy chain, 2-amino-2-deoxy-alpha-D-glucopyranose-(1-2)-alpha-D-glucopyranose-(1-2)-alpha-D-glucopyranose-(1-3)-[alpha-D-galactopyranose-(1-6)]alpha-D-glucopyranose-(1-3)-[L-glycero-alpha-D-manno-heptopyranose-(1-7)]4-O-phosphono-L-glycero-alpha-D-manno-heptopyranose-(1-3)-4-O-phosphono-L-glycero-alpha-D-manno-heptopyranose-(1-5)-[3-deoxy-alpha-D-manno-oct-2-ulopyranosonic acid-(2-4)]3-deoxy-alpha-D-manno-oct-2-ulopyranosonic acid, ... (5 entities in total)
• Functional Keywords: beta barrel, antibody, fab, immune system
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 2
• Total formula weight: 49644.15

Authors

Gomery, K.,Evans, S.V. (deposition date: 2011-12-08, release date: 2012-12-05, Last modification date: 2024-11-27)

Primary citation

Gomery, K.,Muller-Loennies, S.,Brooks, C.L.,Brade, L.,Kosma, P.,Di Padova, F.,Brade, H.,Evans, S.V.
Antibody WN1 222-5 mimics Toll-like receptor 4 binding in the recognition of LPS.
Proc.Natl.Acad.Sci.USA, 109:20877-20882, 2012

PubMed 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.

PubMed: 23184990
DOI: 10.1073/pnas.1209253109

Experimental method

X-RAY DIFFRACTION (1.73 Å)