Structures of the G?-CCT and PhLP1-G?-CCT complexes reveal a mechanism for G-protein ?-subunit folding and G?? dimer assembly.

ABSTRACT: G-protein signaling depends on the ability of the individual subunits of the G-protein heterotrimer to assemble into a functional complex. Formation of the G-protein ?? (G??) dimer is particularly challenging because it is an obligate dimer in which the individual subunits are unstable on their own. Recent studies have revealed an intricate chaperone system that brings G? and G? together. This system includes cytosolic chaperonin containing TCP-1 (CCT; also called TRiC) and its cochaperone phosducin-like protein 1 (PhLP1). Two key intermediates in the G?? assembly process, the G?-CCT and the PhLP1-G?-CCT complexes, were isolated and analyzed by a hybrid structural approach using cryo-electron microscopy, chemical cross-linking coupled with mass spectrometry, and unnatural amino acid cross-linking. The structures show that G? interacts with CCT in a near-native state through interactions of the G?-binding region of G? with the CCT? subunit. PhLP1 binding stabilizes the G? fold, disrupting interactions with CCT and releasing a PhLP1-G? dimer for assembly with G?. This view provides unique insight into the interplay between CCT and a cochaperone to orchestrate the folding of a protein substrate.

SUBMITTER: Plimpton RL 

PROVIDER: S-EPMC4345582 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature