Dataset Information

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

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

Plimpton Rebecca L RL Cuéllar Jorge J Lai Chun Wan J CW Aoba Takuma T Makaju Aman A Franklin Sarah S Mathis Andrew D AD Prince John T JT Carrascosa José L JL Valpuesta José M JM Willardson Barry M BM

Proceedings of the National Academy of Sciences of the United States of America 20150209 8

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 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 Gβ and Gγ together. This system includes cytosolic chaperonin containing TCP-1 (CCT; also called TRiC) and its cochaperone phosd ...[more]

PMID: 25675501

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Project description:Deciphering complete networks of interactions between proteins is the key to comprehend cellular regulatory mechanisms. A significant effort has been devoted to expanding the coverage of the proteome-wide interaction space at molecular level. Although a growing body of research shows that protein docking can, in principle, be used to predict biologically relevant interactions, the accuracy of the across-proteome identification of interacting partners and the selection of near-native complex structures still need to be improved.In this study, we developed a new method to discover and model protein interactions employing an exhaustive all-to-all docking strategy. This approach integrates molecular modeling, structural bioinformatics, machine learning, and functional annotation filters in order to provide interaction data for the bottom-up assembly of protein interaction networks. Encouragingly, the success rates for dimer modeling is 57.5 and 48.7% when experimental and computer-generated monomer structures are employed, respectively. Further, our protocol correctly identifies 81% of protein-protein interactions at the expense of only 19% false positive rate. As a proof of concept, 61,913 protein-protein interactions were confidently predicted and modeled for the proteome of E. coli. Finally, we validated our method against the human immune disease pathway.Protein docking supported by evolutionary restraints and machine learning can be used to reliably identify and model biologically relevant protein assemblies at the proteome scale. Moreover, the accuracy of the identification of protein-protein interactions is improved by considering only those protein pairs co-localized in the same cellular compartment and involved in the same biological process. The modeling protocol described in this communication can be applied to detect protein-protein interactions in other organisms and pathways as well as to construct dimer structures and estimate the confidence of protein interactions experimentally identified with high-throughput techniques.

Dataset Information

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

Publications

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

Similar Datasets

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