Takeda Mitsuhiro, Terasawa Hiroaki, Sakakura Masayoshi, Yamaguchi Yoshiki, Kajiwara Masahiro, Kawashima Hiroto, Miyasaka Masayuki, Shimada Ichio
Graduate School of Pharmaceutical Sciences, the University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
J Biol Chem. 2003 Oct 31;278(44):43550-5. doi: 10.1074/jbc.M308199200. Epub 2003 Aug 19.
CD44 is the main cell surface receptor for hyaluronic acid (HA) and contains a functional HA-binding domain (HABD) composed of a Link module with N- and C-terminal extensions. The contact residues of human CD44 HABD for HA have been determined by cross-saturation experiments and mapped on the topology of CD44 HABD, which we elucidated by NMR. The contact residues are distributed in both the consensus fold for the Link module superfamily and the additional structural elements consisting of the flanking regions. Interestingly, the contact residues exhibit small changes in chemical shift upon HA binding. In contrast, the residues with large chemical shift changes are localized in the C-terminal extension and the first alpha-helix and are generally inconsistent with the contact residues. These results suggest that, upon ligand binding, the C-terminal extension and the first alpha-helix undergo significant conformational changes, which may account for the broad ligand specificity of CD44 HABD.
CD44是透明质酸（HA）的主要细胞表面受体，包含一个由具有N端和C端延伸的Link模块组成的功能性HA结合结构域（HABD）。人CD44 HABD与HA的接触残基已通过交叉饱和实验确定，并映射到CD44 HABD的拓扑结构上，我们通过核磁共振（NMR）阐明了该拓扑结构。接触残基分布在Link模块超家族的共有折叠以及由侧翼区域组成的额外结构元件中。有趣的是，接触残基在与HA结合后化学位移变化很小。相比之下，化学位移变化较大的残基位于C端延伸和第一个α螺旋中，并且通常与接触残基不一致。这些结果表明，在配体结合时，C端延伸和第一个α螺旋会发生显著的构象变化，这可能解释了CD44 HABD广泛的配体特异性。
