Structural basis of adhesion-molecule recognition by ERM proteins revealed by the crystal structure of the radixin-ICAM-2 complex
Structural basis of adhesion-molecule recognition by ERM proteins revealed by the crystal structure of the radixin-ICAM-2 complex
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DOI：
10.1093/emboj/cdg039
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发表时间：
2003-02-03
期刊：
影响因子：
11.4
通讯作者：
Hakoshima, T
中科院分区：
文献类型：
--
作者：
Hamada, K;Shimizu, T;Hakoshima, T
ERM（ezrin/radixin/moesin）蛋白在膜相关细胞骨架的形成过程中识别粘附分子的细胞质结构域。在这里，我们报告了与 ICAM-2 细胞质肽复合的 radixin FERM（4.1 和 ERM）结构域的晶体结构。 ICAM-2 肽的非极性区域包含 RxxTYxVxxA 序列基序，形成一条 β 链，后跟一个短的 3(10) 螺旋。它与磷酸酪氨酸结合 (PTB) 样亚结构域 C 的凹槽结合，由 β-β 关联和多种侧链相互作用介导。 ICAM-2 肽与 FERM 结构域的结合模式不同于包含 NPxY 基序的肽与规范 PTB 结构域的结合模式。基于晶体结构的突变分析揭示了识别的决定因素，并首次深入了解粘附分子和 ERM 蛋白之间的物理联系。
ERM (ezrin/radixin/moesin) proteins recognize the cytoplasmic domains of adhesion molecules in the formation of the membrane-associated cytoskeleton. Here we report the crystal structure of the radixin FERM (4.1 and ERM) domain complexed with the ICAM-2 cytoplasmic peptide. The non-polar region of the ICAM-2 peptide contains the RxxTYxVxxA sequence motif to form a beta-strand followed by a short 3(10)-helix. It binds the groove of the phosphotyrosine-binding (PTB)-like subdomain C mediated by a beta-beta association and several side-chain interactions. The binding mode of the ICAM-2 peptide to the FERM domain is distinct from that of the NPxY motif-containing peptide binding to the canonical PTB domain. Mutation analyses based on the crystal structure reveal the determinant elements of recognition and provide the first insights into the physical link between adhesion molecules and ERM proteins.