한빛사 논문
Abstract
Ho Min Kim,1,7 Beom Seok Park,1,7 Jung-In Kim,1 Sung Eun Kim,1 Judong Lee,2 Se Cheol Oh,1 Purevjav Enkhbayar,4 Norio Matsushima,5 Hayyoung Lee,6 Ook Joon Yoo,2 and Jie-Oh Lee1,3,*
1 Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejon, Korea 305-701
2 Biomedical Research Center, Korea Advanced Institute of Science and Technology, Daejon, Korea 305-701
3 Institute for Bio-Century, Korea Advanced Institute of Science and Technology, Daejon, Korea 305-701
4 Faculty of Biology, National University of Mongolia, Ulaanbaatar, Mongolia
5 School of Health Sciences, Sapporo Medical University, Sapporo, Japan 060-8556
6 Department of Biology, School of Bioscience & Biotechnology, Chungnam National University, Daejon, Korea 305-764
*Corresponding author
Jie-Oh Lee
Summary
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 β 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.
Footnotes
7 These authors contributed equally to this work.
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