2Z62: Crystal Structure Of The Tv3 Hybrid Of Human Tlr4 And Hagfish Vlrb.61

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.
PDB ID: 2Z62Download
MMDB ID: 59978
PDB Deposition Date: 2007/7/22
Updated in MMDB: 2012/11
Experimental Method:
x-ray diffraction
Resolution: 1.7  Å
Similar Structures:
Biological Unit for 2Z62: monomeric; determined by software (PISA)
Molecular Components in 2Z62
Label Count Molecule
Protein (1 molecule)
Toll-like Receptor 4, Variable Lymphocyte Receptor B(Gene symbol: TLR4)
Molecule annotation
Chemicals (9 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB