2Z66

Crystal structure of the VT3 hybrid of human TLR4 and hagfish VLRB.61

Summary for 2Z66

• Entry DOI: 10.2210/pdb2z66/pdb
• Related: 2Z62 2Z63 2Z64 2Z65
• Descriptor: Variable lymphocyte receptor B, Toll-like receptor 4, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: tlr4, toll-like receptor, md-2, lps, leucine-rich repeat, glycoprotein, immune response, inflammatory response, innate immunity, membrane, transmembrane, immune system
• Biological source: Eptatretus burgeri (inshore hagfish, human); More
• Cellular location: Cell membrane ; Single- pass type I membrane protein : O00206
• Total number of polymer chains: 4
• Total formula weight: 146512.37

Authors

Lee, J.-O.,Kim, H.M.,Park, B.S. (deposition date: 2007-07-22, release date: 2007-09-18, Last modification date: 2024-10-23)

Primary citation

Kim, H.M.,Park, B.S.,Kim, J.-I.,Kim, S.E.,Lee, J.,Oh, S.C.,Enkhbayar, P.,Matsushima, N.,Lee, H.,Yoo, O.J.,Lee, J.-O.
Crystal Structure of the TLR4-MD-2 Complex with Bound Endotoxin Antagonist Eritoran
Cell(Cambridge,Mass.), 130:906-917, 2007

PubMed Abstract: 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.

PubMed: 17803912
DOI: 10.1016/j.cell.2007.08.002

Experimental method

X-RAY DIFFRACTION (1.9 Å)