title: Chaperone-mediated assembly of G protein complexes.
abstract: G protein signaling depends on the ability of the individual subunits of the G protein heterotrimer to assemble into functional complexes. Formation of the G protein βγ (Gβγ) 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 the Gβ and Gγ subunits together. This system includes the cytosolic chaperonin containing TCP-1 (CCT) and its co-chaperone phosducin-like protein 1 (PhLP1). CCT assists Gβ in achieving its β-propeller structure, while PhLP1 releases Gβ from CCT and facilitates its interaction with Gγ. Once Gβγ is formed, PhLP1 remains bound until it is displaced by the Gα subunit and the G protein heterotrimer is brought together. Another obligate dimer is the complex between the G protein β(5) subunit and a regulator of G protein signaling protein (Gβ(5)-RGS). Gβ(5)-RGS also requires CCT for Gβ(5) folding, but PhLP1 plays a different role. It stabilizes the interaction between Gβ(5) and CCT, perhaps to increase folding efficiency. After Gβ(5) folding PhLP1 must subsequently release, allowing the RGS protein to bind and form the Gβ(5)-RGS dimer directly on CCT. Gβ(5)-RGS is then freed from CCT to interact with its membrane anchoring protein and form a stable complex that turns off the G protein signal by catalyzing GTP hydrolysis on Gα.
authors.affiliation: Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, 84602, USA, bmwillardson@chem.byu.edu.
authors.forename: Barry M
authors.initials: BM
authors.lastname: Willardson
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Tracy
mesh_terms: D000818:Animals; D044387:GTP-Binding Protein beta Subunits / Q000737:chemistry / Q000378:metabolism*; D044388:GTP-Binding Protein gamma Subunits / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism*; D055503:Protein Multimerization; D015398:Signal Transduction
chemical_list: C118981:G-protein Beta gamma; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D018832:Molecular Chaperones