Shc 磷酸酪氨酸结合结构域的结构与配体识别

Structure and ligand recognition of the phosphotyrosine binding domain of Shc.

作者信息

Zhou M M, Ravichandran K S, Olejniczak E F, Petros A M, Meadows R P, Sattler M, Harlan J E, Wade W S, Burakoff S J, Fesik S W

机构信息

Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, Illinois 60064, USA.

出版信息

Nature. 1995 Dec 7;378(6557):584-92. doi: 10.1038/378584a0.

DOI:10.1038/378584a0

PMID:8524391

Abstract

The nuclear magnetic resonance structure of the phosphotyrosine binding (PTB) domain of Shc complexed to a phosphopeptide reveals an alternative means of recognizing tyrosine-phosphorylated proteins. Unlike in SH2 domains, the phosphopeptide forms an antiparallel beta-strand with a beta-sheet of the protein, interacts with a hydrophobic pocket through the (pY-5) residue, and adopts a beta-turn. The PTB domain is structurally similar to pleckstrin homology domains (a beta-sandwich capped by an alpha-helix) and binds to acidic phospholipids, suggesting a possible role in membrane localization.

摘要

与磷酸肽复合的Shc的磷酸酪氨酸结合（PTB）结构域的核磁共振结构揭示了一种识别酪氨酸磷酸化蛋白的替代方式。与SH2结构域不同，磷酸肽与蛋白的β-折叠形成反平行β-链，通过（pY-5）残基与疏水口袋相互作用，并形成一个β-转角。PTB结构域在结构上与普列克底物蛋白同源结构域（由α-螺旋封闭的β-三明治结构）相似，并与酸性磷脂结合，表明其在膜定位中可能发挥作用。