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Structure and ligand recognition of the phosphotyrosine binding domain of Shc

AUTHORS

Zhou MM , Ravichandran KS , Olejniczak EF , Petros AM , Meadows RP , Sattler M , Harlan JE , Wade WS , Burakoff SJ , Fesik SW . Nature. 1995 12 7; 378(6557). 584-592

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.