Crystal structure of mouse MD-1 with endogenous phospholipid bound in its cavity.
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.
Harada
Hitomi
H
Graduate School of Pharmaceutical Sciences, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Ohto
Umeharu
U
Satow
Yoshinori
Y
D000818:Animals; D000954:Antigens, Surface / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D000954:Antigens, Surface; C113553:Ly86 protein, mouse; D008562:Membrane Glycoproteins; D010743:Phospholipids