| First Author | Kim HM | Year | 2007 |
| Journal | Cell | Volume | 130 |
| Issue | 5 | Pages | 906-17 |
| PubMed ID | 17803912 | Mgi Jnum | J:127195 |
| Mgi Id | MGI:3763315 | Doi | 10.1016/j.cell.2007.08.002 |
| Citation | Kim HM, et al. (2007) Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran. Cell 130(5):906-17 |
| abstractText | 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. |
