State-Targeting Stabilization of Adenosine A_2A Receptor by Fusing a Custom-Made De Novo Designed α-Helical Protein.

ABSTRACT: G-protein coupled receptors (GPCRs) are known for their low stability and large conformational changes upon transitions between multiple states. A widely used method for stabilizing these receptors is to make chimeric receptors by fusing soluble proteins (i.e., fusion partner proteins) into the intracellular loop 3 (ICL3) connecting the transmembrane helices 5 and 6 (TM5 and TM6). However, this fusion approach requires experimental trial and error to identify appropriate soluble proteins, residue positions, and linker lengths for making the fusion. Moreover, this approach has not provided state-targeting stabilization of GPCRs. Here, to rationally stabilize a class A GPCR, adenosine A_2A receptor (A_2AR) in a target state, we carried out the custom-made de novo design o

SUBMITTER: Mitsumoto M 

PROVIDER: S-EPMC8657880 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature