THE 3-DIMENSIONAL SOLUTION STRUCTURE OF THE SRC HOMOLOGY DOMAIN-2 OF THE GROWTH-FACTOR RECEPTOR-BOUND PROTEIN-2

A set of high-resolution three-dimensional solution structures of the Src homology region-2 (SH3) domain of the growth factor receptor-bound protein-2 was determined using heteronuclear NMR spectroscopy. The NM R data used in this study were collected on a stable monomeric protein solution that was free of protein aggregates and proteolysis, The sol ution structure was determined based upon a total of 1439 constraints, which included 1326 nuclear Overhauser effect distance constraints, 7 0 hydrogen bond constraints, and 43 dihedral angle constraints. Distan ce geometry-simulated annealing calculations followed by energy minimi zation yielded a family of 18 structures that converged to a root-mean -square deviation of 1.09 Angstrom for all backbone atoms and 0.40 Ang strom for the backbone atoms of the central beta-sheet. The core struc ture of the SH2 domain contains an antiparallel beta-sheet flanked by two parallel alpha-helices displaying an overall architecture that is similar to other known SH2 domain structures. This family of NMR struc tures is compared to the X-ray structure and to another family of NMR solution structures determined under different solution conditions.