¹H and ¹⁵N assignments and secondary structure of the PI3K SH3 domain

Abstract

The sequential 1 H and 15 N assignments of the SH3 domain of human phosphatidyl inositol 3'‐kinase (PI3K) were determined by a combination of homonuclear and heteronuclear NMR experiments. With the exception of several protons belonging to lysine and proline residues, all proton and proton‐bearing amide nitrogen resonances were assigned. Based on the sequential nuclear Overhauser effects (NOEs), 3 J NH‐CαH coupling constants and locations of slowly exchanging amide protons, we determined that the secondary structures of the protein consists of six β‐strands, two β‐turns and four short helices. Additional long range NOEs indicate that these β‐strands form two antiparallel β‐sheets. The topology of secondary structural elements of the PI3K SH3 domain is similar to those of the SH3 domains from c‐Src and α‐spectrin, suggesting that the SH3 family has a common tertiary structural motif.