2z65

From Proteopedia

Revision as of 11:36, 23 January 2008

Crystal structure of the human TLR4 TV3 hybrid-MD-2-Eritoran complex

Overview

TLR4 and MD-2 form a heterodimer that recognizes LPS (lipopolysaccharide), from Gram-negative bacteria. Eritoran is an analog of LPS that antagonizes, its activity by binding to the TLR4-MD-2 complex. We determined the, structure of the full-length ectodomain of the mouse TLR4 and MD-2, complex. We also produced a series of hybrids of human TLR4 and hagfish, VLR and determined their structures with and without bound MD-2 and, Eritoran. TLR4 is an atypical member of the LRR family and is composed of, N-terminal, central, and C-terminal domains. The beta sheet of the central, domain shows unusually small radii and large twist angles. MD-2 binds to, the concave surface of the N-terminal and central domains. The interaction, with Eritoran is mediated by a hydrophobic internal pocket in MD-2. Based, on structural analysis and mutagenesis experiments on MD-2 and TLR4, we, propose a model of TLR4-MD-2 dimerization induced by LPS.

About this Structure

2Z65 is a Protein complex structure of sequences from Homo sapiens and Homo sapiens, eptatretus burgeri with , and as ligands. Full crystallographic information is available from OCA.

Reference

Crystal Structure of the TLR4-MD-2 Complex with Bound Endotoxin Antagonist Eritoran., Kim HM, Park BS, Kim JI, Kim SE, Lee J, Oh SC, Enkhbayar P, Matsushima N, Lee H, Yoo OJ, Lee JO, Cell. 2007 Sep 7;130(5):906-17. PMID:17803912

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