Structures of the Cd44-hyaluronan complex provide insight into a fundamental carbohydrate-protein interaction
Structures of the Cd44-hyaluronan complex provide insight into a fundamental carbohydrate-protein interaction
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DOI：
10.1038/nsmb1201
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发表时间：
2007-03-01
影响因子：
16.8
通讯作者：
Jackson, David G.
中科院分区：
文献类型：
--
作者：
Banerji, Suneale;Wright, Alan J.;Jackson, David G.
调节细胞和普遍存在的基质糖胺聚糖透明质酸之间的瞬时相互作用对胚胎发育和白细胞归巢等基本过程至关重要。Cd 44是透明质酸的主要细胞表面受体，通过称为连接模块的凝集素样折叠结合配体，但仅在适当的功能活化后。Cd 44-透明质酸相互作用的分子细节以及这种激活的结构基础尚不清楚。在这里，我们提出的第一个晶体结构的镉44与透明质酸复合。这表明与透明质酸的相互作用主要由形状和氢键互补性决定，并确定了两种构象形式的受体，其在关键的透明质酸结合残基（Arg 45，相当于人CD 44中的Arg 41）的方向上不同。通过NMR测量表明，可以诱导的构象转变透明质酸结合，提供进一步了解可能的机制调节镉44。
Regulation of transient interactions between cells and the ubiquitous matrix glycosaminoglycan hyaluronan is crucial to such fundamental processes as embryonic development and leukocyte homing. Cd44, the primary cell surface receptor for hyaluronan, binds ligand via a lectin-like fold termed the Link module, but only after appropriate functional activation. The molecular details of the Cd44-hyaluronan interaction and hence the structural basis for this activation are unknown. Here we present the first crystal structure of Cd44 complexed with hyaluronan. This reveals that the interaction with hyaluronan is dominated by shape and hydrogen-bonding complementarity and identifies two conformational forms of the receptor that differ in orientation of a crucial hyaluronan-binding residue (Arg45, equivalent to Arg41 in human CD44). Measurements by NMR indicate that the conformational transition can be induced by hyaluronan binding, providing further insight into possible mechanisms for regulation of Cd44.