Crystal structure of mouse MD-1 with endogenous phospholipid bound in its cavity

J Mol Biol. 2010 Jul 23;400(4):838-46. doi: 10.1016/j.jmb.2010.05.063. Epub 2010 Jun 1.

Abstract

MD-1 is a glycoprotein that associates with a B-cell-specific RP105 protein and has a low sequence identity of 16% to MD-2 that associates with Toll-like receptor 4 and recognizes endotoxic lipopolysaccharide. MD-1 and RP105 are supposed to mediate lipopolysaccharide recognition; however, little is known about their structures and functions. Here, the crystal structure of mouse MD-1 is determined at 1.65 A resolution. MD-1 has a hydrophobic cavity sandwiched by two beta-sheets as is MD-2. The cavity is 25 A long, 5 A wide, and 10 A deep: longer, narrower, and shallower than that of MD-2. No charged residues are located on the cavity entrance. MD-1 is primarily monomeric in solution but shows a dimeric assembly in the crystal lattices, with their cavity entrances facing each other. In the cavity, electron densities attributable to phosphatidylcholine are located. Together with the binding assay with tetra-acylated lipid IVa, MD-1 is shown to be a lipid-binding coreceptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Surface / chemistry*
  • Antigens, Surface / metabolism*
  • Binding Sites
  • Crystallography, X-Ray
  • Dimerization
  • Membrane Glycoproteins / chemistry*
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Phospholipids / chemistry*
  • Phospholipids / metabolism*
  • Protein Binding
  • Protein Structure, Quaternary
  • Protein Structure, Secondary
  • Protein Structure, Tertiary

Substances

  • Antigens, Surface
  • Ly86 protein, mouse
  • Membrane Glycoproteins
  • Phospholipids

Associated data

  • PDB/3M7O