Structural and dynamic effects of cholesterol at preferred sites of interaction with rhodopsin identified from microsecond length molecular dynamics simulations.

ABSTRACT: An unresolved question about GPCR function is the role of membrane components in receptor stability and activation. In particular, cholesterol is known to affect the function of membrane proteins, but the details of its effect on GPCRs are still elusive. Here, we describe how cholesterol modulates the behavior of the TM1-TM2-TM7-helix 8(H8) functional network that comprises the highly conserved NPxxY(x)(5,6)F motif, through specific interactions with the receptor. The inferences are based on the analysis of microsecond length molecular dynamics (MD) simulations of rhodopsin in an explicit membrane environment. Three regions on the rhodopsin exhibit the highest cholesterol density throughout the trajectory: the extracellular end of TM7, a location resembling the high-density sterol area fro

SUBMITTER: Khelashvili G 

PROVIDER: S-EPMC4101808 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature