CRYSTAL-STRUCTURE OF THE MAMMALIAN GRB2 ADAPTER

The mammalian growth factor receptor- binding protein Grb2 is an adapt or that mediates activation of guanine nucleotide exchange on Ras. Grb 2 binds to the receptor through its SH2 domain and to the carboxyl-ter minal domain of Son of sevenless through its two SH3 domains. It is th us a key element in the signal transduction pathway. The crystal struc ture of Grb2 was determined to 3.1 angstrom resolution. The asymmetric unit is composed of an embedded dimer. The interlaced junctions betwe en the SH2 and SH3 domains bring the two adjacent faces of the SH3 dom ains in van der Waals contact but leave room for the binding of prolin e-rich peptides.