The SH3 domain of Eps8 exists as a novel intertwined dimer

K. Y. Radha Kishan, Vanderbilt University School of Medicine
Giorgio Scita, Istituto Europeo di Oncologia
William T. Wong, National Institute of Dental and Craniofacial Research (NIDCR)
Pier Paolo Di Fiore, Istituto Europeo di Oncologia
Marcia E. Newcomer, Vanderbilt University School of Medicine


SH3 domains are structurally well-characterized as monomeric modular units of protein structure that mediate protein-protein recognition in numerous signal transduction proteins. The X-ray crystallographic structure of the Eps8 SH3 domain reveals a novel variation of the canonical SH3 fold: the SH3 domain from Eps8 is a dimer formed by strand interchange. In addition, co-immunoprecipitation experiments show that intact Eps8 is multimeric in vivo. Hence, the SH3 domain of Eps8 may represent a dimerization motif.