Cholesterol modulates the dimer interface of the β₂-adrenergic receptor via cholesterol occupancy sites.

ABSTRACT: The β2-adrenergic receptor is an important member of the G-protein-coupled receptor (GPCR) superfamily, whose stability and function are modulated by membrane cholesterol. The recent high-resolution crystal structure of the β2-adrenergic receptor revealed the presence of possible cholesterol-binding sites in the receptor. However, the functional relevance of cholesterol binding to the receptor remains unexplored. We used MARTINI coarse-grained molecular-dynamics simulations to explore dimerization of the β2-adrenergic receptor in lipid bilayers containing cholesterol. A novel (to our knowledge) aspect of our results is that receptor dimerization is modulated by membrane cholesterol. We show that cholesterol binds to transmembrane helix IV, and cholesterol occupancy at this site restricts i

SUBMITTER: Prasanna X 

PROVIDER: S-EPMC3984991 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature