Dynamic spatiotemporal determinants modulate GPCR:G protein coupling selectivity and promiscuity.

ABSTRACT: Recent studies have shown that G protein coupled receptors (GPCRs) show selective and promiscuous coupling to different Gα protein subfamilies and yet the mechanisms of the range of coupling preferences remain unclear. Here, we use Molecular Dynamics (MD) simulations on ten GPCR:G protein complexes and show that the location (spatial) and duration (temporal) of intermolecular contacts at the GPCR:Gα protein interface play a critical role in how GPCRs selectively interact with G proteins. We identify that some GPCR:G protein interface contacts are common across Gα subfamilies and others specific to Gα subfamilies. Using large scale data analysis techniques on the MD simulation snapshots we derive a spatio-temporal code for contacts that confer G protein selective coupling and validated thes

SUBMITTER: Sandhu M 

PROVIDER: S-EPMC9718833 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature