2Z64

Crystal structure of mouse TLR4 and mouse MD-2 complex

Summary for 2Z64

• Entry DOI: 10.2210/pdb2z64/pdb
• Related: 2Z62 2Z63 2Z65 2Z66
• Descriptor: Toll-like receptor 4, Lymphocyte antigen 96, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: tlr4, toll-like receptor, md-2, lps, disease mutation, glycoprotein, immune response, inflammatory response, innate immunity, leucine-rich repeat, membrane, transmembrane, secreted, immune system
• Biological source: Mus musculus (house mouse); More
• Cellular location: Membrane; Single-pass type I membrane protein (By similarity): Q9QUK6; Secreted, extracellular space: Q9JHF9
• Total number of polymer chains: 2
• Total formula weight: 87782.21

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 (2.84 Å)