Crystal structure of the PEG-bound SH3 domain of myosin IB fromEntamoeba histolyticareveals its mode of ligand recognition

Abstract

The versatility in the recognition of various interacting proteins by the SH3 domain drives a variety of cellular functions. Here, the crystal structure of the C-terminal SH3 domain of myosin IB fromEntamoeba histolytica(EhMySH3) is reported at a resolution of 1.7 Å in native and PEG-bound states. Comparisons with other structures indicated that the PEG molecules occupy protein–protein interaction pockets similar to those occupied by the peptides in other peptide-bound SH3-domain structures. Also, analysis of the PEG-boundEhMySH3 structure led to the recognition of two additional pockets, apart from the conventional polyproline and specificity pockets, that are important for ligand interaction. Molecular-docking studies combined with various comparisons revealed structural similarity betweenEhMySH3 and the SH3 domain of β-Pix, and this similarity led to the prediction thatEhMySH3 preferentially binds targets containing type II-like PXXP motifs. These studies expand the understanding of theEhMySH3 domain and provide extensive structural knowledge, which is expected to help in predicting the interacting partners which function together with myosin IB during phagocytosis inE. histolyticainfections.