02148nas a2200169   4500008004100000022001400041245011300055210006900168260007900237300001400316490000800330520144400338100002101782700002801803700002001831856012701851       2014                        eng d  a0006-349500aCholesterol modulates the dimer interface of the beta(2)-adrenergic receptor via cholesterol occupancy sites0 aCholesterol modulates the dimer interface of the beta2adrenergic  a600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USAbCELL PRESScMAR  a1290-13000 v1063 a<p>The beta(2)-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 beta(2)-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 beta(2)-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 its involvement at the dimer interface. With increasing cholesterol concentration, an increased presence of transmembrane helices I and II, but a reduced presence of transmembrane helix IV, is observed at the dimer interface. To our knowledge, this study is one of the first to explore the correlation between cholesterol occupancy and GPCR organization. Our results indicate that dimer plasticity is relevant not just as an organizational principle but also as a subtle regulatory principle for GPCR function. We believe these results constitute an important step toward designing better drugs for GPCR dimer targets.</p>1 aPrasanna, Xavier1 aChattopadhyay, Amitabha1 aSengupta, Durba  uhttps://library.ncl.res.in/content/cholesterol-modulates-dimer-interface-beta2-adrenergic-receptor-cholesterol-occupancy-0