Sulfotyrosine, an interaction specificity determinant for extracellular protein-protein interactions

Abstract

Tyrosine sulfation, a post-translational modification, can enhance and often determine protein-protein interaction specificity. Sulfotyrosyl residues (sTyr) are formed by tyrosylprotein sulfotransferase during maturation in the golgi apparatus, and most often occur singly or as a cluster of two or three sTyr within a six-residue span. With both negative charge and aromatic character, sTyr enables numerous atomic contacts as visualized in binding interface structural models, and so there is no discernible binding site consensus. Found exclusively in secreted proteins, sTyr residues occur in four broad sequence contexts. First, a single sTyr residue is critical for diverse high-affinity interactions between peptide hormones and their receptor in both plants and animals. Second, sTyr clusters within structurally flexible anionic segments are essential for a variety of processes including coreceptor binding to the HIV-1 envelope spike protein during virus entry, chemokine interactions with many chemokine receptors, and leukocyte rolling cell adhesion.