Graduate School of Pharmaceutical Sciences, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
J Mol Biol. 2010 Jul 23;400(4):838-46. doi: 10.1016/j.jmb.2010.05.063. Epub 2010 Jun 1.
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.
MD-1 是一种糖蛋白，与 B 细胞特异性的 RP105 蛋白结合，与识别内毒素脂多糖的 Toll 样受体 4 结合的 MD-2 具有 16%的低序列同一性。MD-1 和 RP105 被认为介导脂多糖的识别；然而，它们的结构和功能知之甚少。在这里，我们测定了小鼠 MD-1 的晶体结构，分辨率为 1.65A。MD-1 具有由两个β-折叠夹在中间的疏水性腔，就像 MD-2 一样。腔长 25A，宽 5A，深 10A：比 MD-2 更长、更窄、更浅。腔入口处没有带电荷的残基。MD-1 在溶液中主要以单体形式存在，但在晶体晶格中显示出二聚体组装，其腔入口彼此相对。在腔中，可归因于磷脂酰胆碱的电子密度被定位。结合四酰化脂质 IVa 的结合实验表明，MD-1 是一种脂质结合共受体。
