6VU8

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

6VU8 の概要

• エントリーDOI: 10.2210/pdb6vu8/pdb
• 関連するPDBエントリー: 6VU5
• EMDBエントリー: 21387 21388
• 分子名称: Resistance to inhibitors of cholinesterase 8 homolog A (C. elegans), Guanine nucleotide-binding protein G(i) subunit alpha-1 (2 entities in total)
• 機能のキーワード: 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
• 由来する生物種: Rattus norvegicus (Rat); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 101624.81

構造登録者

Seven, A.B.,Hilger, D. (登録日: 2020-02-14, 公開日: 2020-03-18, 最終更新日: 2025-05-28)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (4.14 Å)