Unifying view of mechanical and functional hotspots across class A GPCRs.

ABSTRACT: G protein-coupled receptors (GPCRs) are the largest superfamily of signaling proteins. Their activation process is accompanied by conformational changes that have not yet been fully uncovered. Here, we carry out a novel comparative analysis of internal structural fluctuations across a variety of receptors from class A GPCRs, which currently has the richest structural coverage. We infer the local mechanical couplings underpinning the receptors' functional dynamics and finally identify those amino acids whose virtual deletion causes a significant softening of the mechanical network. The relevance of these amino acids is demonstrated by their overlap with those known to be crucial for GPCR function, based on static structural criteria. The differences with the latter set allow us to identify

SUBMITTER: Ponzoni L 

PROVIDER: S-EPMC5315405 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature