A STRUCTURAL EXPLANATION FOR THE RECOGNITION OF TYROSINE-BASED ENDOCYTOTIC SIGNALS

Many cell surface proteins are marked for endocytosis by a cytoplasmic sequence motif, tyrosine-X-X-(hydrophobic residue), that is recognize d by the mu 2 subunit of AP2 adaptors. Crystal structures of the inter nalization signal binding domain of mu 2 complexed with the internaliz ation signal peptides of epidermal growth factor receptor and the tran s-Golgi network protein TGN38 have been determined at 2.7 angstrom res olution, The signal peptides adopted an extended conformation rather t han the expected tight turn, Specificity was conferred by hydrophobic pockets that bind the tyrosine and leucine in the peptide. In the crys tal, the protein forms dimers that could increase the strength and spe cificity of binding to dimeric receptors.