On the importance of a funneled energy landscape for the assembly and regulation of multidomain Src tyrosine kinases.

ABSTRACT: Regulation of signaling pathways in the cell often involves multidomain allosteric enzymes that are able to adopt alternate active or inactive conformations in response to specific stimuli. It is therefore of great interest to elucidate the energetic and structural determinants that govern the conformational plasticity of these proteins. In this study, free-energy computations have been used to address this fundamental question, focusing on one important family of signaling enzymes, the Src tyrosine kinases. Inactivation of these enzymes depends on the formation of an assembly comprising a tandem of SH3 and SH2 modules alongside a catalytic domain. Activation results from the release of the SH3 and SH2 domains, which are then believed to be structurally uncoupled by virtue of a flexible pe

SUBMITTER: Faraldo-Gomez JD 

PROVIDER: S-EPMC1959435 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature