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TitleStructures of Gα Proteins in Complex with Their Chaperone Reveal Quality Control Mechanisms.
Journal, issue, pagesCell Rep, Vol. 30, Issue 11, Page 3699-33709.e6, Year 2020
Publish dateMar 17, 2020
AuthorsAlpay Burak Seven / Daniel Hilger / Makaía M Papasergi-Scott / Li Zhang / Qianhui Qu / Brian K Kobilka / Gregory G Tall / Georgios Skiniotis /
PubMed AbstractMany chaperones promote nascent polypeptide folding followed by substrate release through ATP-dependent conformational changes. Here we show cryoEM structures of Gα subunit folding intermediates in ...Many chaperones promote nascent polypeptide folding followed by substrate release through ATP-dependent conformational changes. Here we show cryoEM structures of Gα subunit folding intermediates in complex with full-length Ric-8A, a unique chaperone-client system in which substrate release is facilitated by guanine nucleotide binding to the client G protein. The structures of Ric-8A-Gα and Ric-8A-Gα complexes reveal that the chaperone employs its extended C-terminal region to cradle the Ras-like domain of Gα, positioning the Ras core in contact with the Ric-8A core while engaging its switch2 nucleotide binding region. The C-terminal α5 helix of Gα is held away from the Ras-like domain through Ric-8A core domain interactions, which critically depend on recognition of the Gα C terminus by the chaperone. The structures, complemented with biochemical and cellular chaperoning data, support a folding quality control mechanism that ensures proper formation of the C-terminal α5 helix before allowing GTP-gated release of Gα from Ric-8A.
External linksCell Rep / PubMed:32126208 / PubMed Central
MethodsEM (single particle)
Resolution3.5 - 4.14 Å
Structure data

EMDB-21387, PDB-6vu5:
Structure of G-alpha-q bound to its chaperone Ric-8A
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-21388, PDB-6vu8:
Structure of G-alpha-i bound to its chaperone Ric-8A
Method: EM (single particle) / Resolution: 4.14 Å

Source
  • Rattus norvegicus/Homo sapiens (Norway rat)
  • rattus norvegicus (Norway rat)
  • homo sapiens (human)
KeywordsCHAPERONE / G protein alpha subunit / Ric-8; molecular chaperone; G alpha folding; guanine nucleotide exchange factor (GEF); cryoEM structure; protein complex; G protein-coupled receptor (GPCR) / phosphorylation; quality control.

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