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TitleStructure of the G protein chaperone and guanine nucleotide exchange factor Ric-8A bound to Gαi1.
Journal, issue, pagesNat Commun, Vol. 11, Issue 1, Page 1077, Year 2020
Publish dateFeb 26, 2020
AuthorsLevi 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 AbstractRic-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 linksNat Commun / PubMed:32103024 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution3.3 - 3.87 Å
Structure data

20812

6ukt

EMDB-20812, PDB-6ukt:
Cryo-EM structure of mammalian Ric-8A:Galpha(i):nanobody complex
Method: EM (single particle) / Resolution: 3.87 Å

PDB-6tyl:
Crystal structure of mammalian Ric-8A:Galpha(i):nanobody complex
Method: X-RAY DIFFRACTION / Resolution: 3.3 Å

Source
  • rattus norvegicus (Norway rat)
  • lama glama (llama)
KeywordsSIGNALING PROTEIN / Ric-8A / G protein / GEF

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