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-Structure paper
Title | Structures of Gα Proteins in Complex with Their Chaperone Reveal Quality Control Mechanisms. |
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Journal, issue, pages | Cell Rep, Vol. 30, Issue 11, Page 3699-33709.e6, Year 2020 |
Publish date | Mar 17, 2020 |
Authors | Alpay Burak Seven / Daniel Hilger / Makaía M Papasergi-Scott / Li Zhang / Qianhui Qu / Brian K Kobilka / Gregory G Tall / Georgios Skiniotis / |
PubMed Abstract | 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 ...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 links | Cell Rep / PubMed:32126208 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.5 - 4.14 Å |
Structure data | EMDB-21387, PDB-6vu5: EMDB-21388, PDB-6vu8: |
Source |
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Keywords | CHAPERONE / 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. |