Enabling STD-NMR fragment screening using stabilized native GPCR: A case study of adenosine receptor.

ABSTRACT: Structural studies of integral membrane proteins have been limited by the intrinsic conformational flexibility and the need to stabilize the proteins in solution. Stabilization by mutagenesis was very successful for structural biology of G protein-coupled receptors (GPCRs). However, it requires heavy protein engineering and may introduce structural deviations. Here we describe the use of specific calixarenes-based detergents for native GPCR stabilization. Wild type, full length human adenosine A_2A receptor was used to exemplify the approach. We could stabilize native, glycosylated, non-aggregated and homogenous A_2AR that maintained its ligand binding capacity. The benefit of the preparation for fragment screening, using the Saturation-Transfer Difference nuclear magne

SUBMITTER: Igonet S 

PROVIDER: S-EPMC5970182 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature