2z62

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Template:STRUCTURE 2z62

Crystal structure of the TV3 hybrid of human TLR4 and hagfish VLRB.61

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

2Z62 is a Single protein structure of sequence from Homo sapiens, eptatretus burgeri. 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 Page seeded by OCA on Sun May 4 19:59:21 2008