|Title||From Binding-Induced Dynamic Effects in SH3 Structures to Evolutionary Conserved Sectors|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Ruano, AZafra, Cilia, E, Couceiro, JR, Sanz, JRuiz, Schymkowitz, J, Rousseau, F, Luque, I, Lenaerts, T|
|Journal||PLoS Comput Biol|
Small protein domains as Src Homology 3 often act as docking sites and serve as regulatory elements. To understand their role in the regulation of a protein’s activity, one needs to understand how their backbone and sidechain dynamics are affected when binding to peptides. We have therefore computationally analyzed eight different SH3 domain structures, predicting dynamical effects induced by binding through our MCIT approach that has been shown to correlate well with experimental data. We show first that binding the Src SH3 domain triggers a particular cascade of dynamic effects, which are compatible with an induced fit mechanism reported before. We then combined the predictions for the eight SH3 domains into different consensus models, with the aim of analyzing, for the first time from a structural perspective, commonalities and differences in the transduction mechanisms among these SH3 domains. These consensus results are, on one hand, in agreement with the domain sectors recently identified for the entire family of SH3 domains. On the other hand, they reveal also that differences exist between the different subgroups that were studied here, requiring extensive experimental investigations of the importance of these differences for the proteins wherein these SH3 domains can be found.
From Binding-Induced Dynamic Effects in SH3 Structures to Evolutionary Conserved Sectors
Posted on Friday, September 2, 2016