Modulation of adenosine A2a receptor oligomerization by receptor activation and PIP₂ interactions.

ABSTRACT: GPCRs have been shown to form oligomers, which generate distinctive signaling outcomes. However, the structural nature of the oligomerization process remains uncertain. We have characterized oligomeric configurations of the adenosine A2a receptor (A2aR) by combining large-scale molecular dynamics simulations with Markov state models. These oligomeric structures may also serve as templates for studying oligomerization of other class A GPCRs. Our simulation data revealed that receptor activation results in enhanced oligomerization, more diverse oligomer populations, and a more connected oligomerization network. The active state conformation of the A2aR shifts protein-protein association interfaces to those involving intracellular loop ICL3 and transmembrane helix TM6. Binding of PIP₂

SUBMITTER: Song W 

PROVIDER: S-EPMC8581623 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature