How Do Short Chain Nonionic Detergents Destabilize G-Protein-Coupled Receptors?

ABSTRACT: Stability of detergent-solubilized G-protein-coupled receptors (GPCRs) is crucial for their purification in a biologically relevant state, and it is well-known that short chain detergents such as octylglucoside are more denaturing than long chain detergents such as dodecylmaltoside. However, the molecular basis for this phenomenon is poorly understood. To gain insights into the mechanism of detergent destabilization of GPCRs, we used atomistic molecular dynamics simulations of thermostabilized adenosine receptor (A_2AR) mutants embedded in either a lipid bilayer or detergent micelles of alkylmaltosides and alkylglucosides. A_2AR mutants in dodecylmaltoside or phospholipid showed low flexibility and good interhelical packing. In contrast, A_2AR mutants in eithe

SUBMITTER: Lee S 

PROVIDER: S-EPMC5148649 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature