6VU8

Structure of G-alpha-i bound to its chaperone Ric-8A

Summary for 6VU8

• Entry DOI: 10.2210/pdb6vu8/pdb
• Related: 6VU5
• EMDB information: 21387 21388
• Descriptor: Resistance to inhibitors of cholinesterase 8 homolog A (C. elegans), Guanine nucleotide-binding protein G(i) subunit alpha-1 (2 entities in total)
• Functional Keywords: 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., chaperone
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 2
• Total formula weight: 101624.81

Authors

Seven, A.B.,Hilger, D. (deposition date: 2020-02-14, release date: 2020-03-18, Last modification date: 2024-10-23)

Primary citation

Seven, A.B.,Hilger, D.,Papasergi-Scott, M.M.,Zhang, L.,Qu, Q.,Kobilka, B.K.,Tall, G.G.,Skiniotis, G.
Structures of G alpha Proteins in Complex with Their Chaperone Reveal Quality Control Mechanisms.
Cell Rep, 30:3699-3709.e6, 2020

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 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.

PubMed: 32126208
DOI: 10.1016/j.celrep.2020.02.086

Experimental method

ELECTRON MICROSCOPY (4.14 Å)