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-Structure paper
Title | Structure of the G protein chaperone and guanine nucleotide exchange factor Ric-8A bound to Gαi1. |
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Journal, issue, pages | Nat Commun, Vol. 11, Issue 1, Page 1077, Year 2020 |
Publish date | Feb 26, 2020 |
Authors | Levi J McClelland / Kaiming Zhang / Tung-Chung Mou / Jake Johnston / Cindee Yates-Hansen / Shanshan Li / Celestine J Thomas / Tzanko I Doukov / Sarah Triest / Alexandre Wohlkonig / Gregory G Tall / Jan Steyaert / Wah Chiu / Stephen R Sprang / |
PubMed Abstract | Ric-8A is a cytosolic Guanine Nucleotide exchange Factor (GEF) that activates heterotrimeric G protein alpha subunits (Gα) and serves as an essential Gα chaperone. Mechanisms by which Ric-8A ...Ric-8A is a cytosolic Guanine Nucleotide exchange Factor (GEF) that activates heterotrimeric G protein alpha subunits (Gα) and serves as an essential Gα chaperone. Mechanisms by which Ric-8A catalyzes these activities, which are stimulated by Casein Kinase II phosphorylation, are unknown. We report the structure of the nanobody-stabilized complex of nucleotide-free Gα bound to phosphorylated Ric-8A at near atomic resolution by cryo-electron microscopy and X-ray crystallography. The mechanism of Ric-8A GEF activity differs considerably from that employed by G protein-coupled receptors at the plasma membrane. Ric-8A engages a specific conformation of Gα at multiple interfaces to form a complex that is stabilized by phosphorylation within a Ric-8A segment that connects two Gα binding sites. The C-terminus of Gα is ejected from its beta sheet core, thereby dismantling the GDP binding site. Ric-8A binds to the exposed Gα beta sheet and switch II to stabilize the nucleotide-free state of Gα. |
External links | Nat Commun / PubMed:32103024 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 3.3 - 3.87 Å |
Structure data | EMDB-20812, PDB-6ukt: PDB-6tyl: |
Source |
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Keywords | SIGNALING PROTEIN / Ric-8A / G protein / GEF |