Dynamic Coupling and Allosteric Networks in the α Subunit of Heterotrimeric G Proteins.

ABSTRACT: G protein α subunits cycle between active and inactive conformations to regulate a multitude of intracellular signaling cascades. Important structural transitions occurring during this cycle have been characterized from extensive crystallographic studies. However, the link between observed conformations and the allosteric regulation of binding events at distal sites critical for signaling through G proteins remain unclear. Here we describe molecular dynamics simulations, bioinformatics analysis, and experimental mutagenesis that identifies residues involved in mediating the allosteric coupling of receptor, nucleotide, and helical domain interfaces of Gαi. Most notably, we predict and characterize novel allosteric decoupling mutants, which display enhanced helical domain opening, increased

SUBMITTER: Yao XQ 

PROVIDER: S-EPMC4813496 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature