CRYSTAL-STRUCTURE OF THE SH2 DOMAIN FROM THE ADAPTER PROTEIN SHC - A MODEL FOR PEPTIDE BINDING BASED ON X-RAY AND NMR DATA
CRYSTAL-STRUCTURE OF THE SH2 DOMAIN FROM THE ADAPTER PROTEIN SHC - A MODEL FOR PEPTIDE BINDING BASED ON X-RAY AND NMR DATA
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DOI：
10.1006/jmbi.1995.0601
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发表时间：
1995-11-17
影响因子：
5.6
通讯作者：
HOMMEL, U
中科院分区：
文献类型：
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作者：
MIKOL, V;BAUMANN, G;HOMMEL, U
Src同源2结构域（SH 2）是在多种细胞质信号传导分子内发现的蛋白模块，其以高亲和力结合含磷酸酪氨酸（pY）的蛋白序列。我们在这里报告的晶体结构的SH 2结构域的衔接蛋白SHC（她），这已被细化的限制最小二乘法的X-因子为17.3%至2.7埃。总体She结构基本上类似于在其他SH 2结构域中确定的结构，但其在环的数量上显示出显著差异，从而提供了没有明显次级口袋的分子表面。基于知识的蛋白质的晶体结构的模型，低亲和力的她结合肽已产生的核磁共振数据在溶液中使用转移核Overhauser增强作为分子内距离的限制。该模型表明，酪氨酸部分结合她在一个相当类似的方式观察到的其他SH 2-肽复合物，但在位置+3的残基似乎不与蛋白质进行特异性接触。分子间晶体相互作用发生在pY-结合位点和C-末端残基之间的一个pY-相关分子。这种晶体堆积相互作用表明抑制性调节如何在SHC活性中发挥作用。
Src homology 2 domains (SH2) are protein modules found within a wide variety of cytoplasmic signalling molecules that bind with high affinity to phosphotyrosyl (pY)-containing protein sequences. We report here the crystal structure of the SH2 domain from the adaptor protein SHC (She), which has been refined by restrained least-squares methods to an X-factor of 17.3% to 2.7 Angstrom. The overall She architecture is essentially similar to that determined in other SH2 domains but it shows significant differences in a number of loops, thus providing a molecular surface With no obvious secondary pocket. Based on the knowledge of the crystal structure of the protein a model for a low affinity She-bound peptide has been generated from nuclear magnetic resonance data in solution using transferred nuclear Overhauser enhancements as intramolecular distance restraints. The model shows that the tyrosine moiety binds She in a rather similar way to that observed for other SH2-peptide complexes, but that the residue in position +3 does not seem to make specific contact with the protein. An intermolecular crystallographic interaction occurs between the pY-binding site and the C-terminal residues of a symmetry-related molecule. This crystal packing interaction suggests how inhibitory regulation could play a role in SHC activity.