Secondary structure of Src homology 2 domain of c-Abl by heteronouclear NMR spectroscopy in solution

Abstract

The Src homology 2 (SH2) domain is a recognition motif thought to mediate the association of the cytoplasmic proteins involved in signal transduction by binding to phosphotyrosyl-containing sequences in proteins. Assignments of nearly all 1H and 15N resonances of the SH2 domain from the c-Abl protein-tyrosine kinase have been obtained from homonuclear and heteronuclear NMR experiments. The secondary structure has been elucidated from the pattern of nuclear Overhauser effects, from vicinal coupling constants, and from observation of slowly exchanging amino hydrogens. The secondary structure contains two α-helices and eight β-strands, six of which are arranged in two contiguous, antiparallel β-sheets. Residues believed to be involved in phosphotyrosyl ligand binding are on a face of one β-sheet. The alignment of homologous sequences on the basis of secondary structure suggests a conserved global fold in a family of SH2 domains.