SH3-SH2 Domain Orientation in Src Kinases: NMR Studies of Fyn

• Published in: Structure (London) Vol. 10; no. 7; pp. 901 - 911
• Main Authors: Ulmer, Tobias S, Werner, Jörn M, Campbell, Iain D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2002
• Subjects: domain orientation; dynamic domain coupling; Humans; Ligands; Magnetic Resonance Spectroscopy; Models, Molecular; Peptides - chemistry; Proto-Oncogene Proteins - chemistry; Proto-Oncogene Proteins c-fyn; residual dipolar coupling; rotational diffusion anisotropy; SH3-SH2; src Homology Domains; Src kinase; src-Family Kinases - chemistry; residual dipolar coupling; SH3-SH2; Src kinase; domain orientation; dynamic domain coupling; rotational diffusion anisotropy
• ISSN: 0969-2126; 1878-4186
• DOI: 10.1016/S0969-2126(02)00781-5

The regulatory domains of Src family kinases SH3 and SH2 suppress Src activity when bound to the catalytic domain. Here, the isolated SH3-SH2 fragment from the Src family member Fyn (FynSH32) is studied by NMR. The properties of this fragment are expected to be similar to the domains in the active state, where they are dissociated from the catalytic domain. Crosscommunication between SH3 and SH2 of FynSH32, measured by chemical shift perturbation, was found to be small. Diffusion and alignment anisotropy measurements showed that SH3 and SH2 of peptide-bound FynSH32 are significantly coupled but still exhibit some interdomain flexibility. The observed average domain orientation indicates that a large SH3-SH2 domain closure is required to reach the inactive state. The implications of these results for Src regulation are discussed.