7TM3

Structure of the rabbit 80S ribosome stalled on a 2-TMD Rhodopsin intermediate in complex with the multipass translocon

これはPDB形式変換不可エントリーです。

7TM3 の概要

• エントリーDOI: 10.2210/pdb7tm3/pdb
• EMDBエントリー: 25994
• 分子名称: uL2, uL5, eL13, ... (56 entities in total)
• 機能のキーワード: ribosome, membrane protein, translocon
• 由来する生物種: Oryctolagus cuniculus (rabbit); 詳細
• タンパク質・核酸の鎖数: 54
• 化学式量合計: 2356140.87

構造登録者

Kim, M.K.,Lewis, A.J.O.,Keenan, R.J.,Hegde, R.S. (登録日: 2022-01-19, 公開日: 2022-10-19, 最終更新日: 2024-06-05)

主引用文献

Smalinskaite, L.,Kim, M.K.,Lewis, A.J.O.,Keenan, R.J.,Hegde, R.S.
Mechanism of an intramembrane chaperone for multipass membrane proteins.
Nature, 611:161-166, 2022

PubMed Abstract: Multipass membrane proteins play numerous roles in biology and include receptors, transporters, ion channels and enzymes. How multipass proteins are co-translationally inserted and folded at the endoplasmic reticulum is not well understood. The prevailing model posits that each transmembrane domain (TMD) of a multipass protein successively passes into the lipid bilayer through a front-side lateral gate of the Sec61 protein translocation channel. The PAT complex, an intramembrane chaperone comprising Asterix and CCDC47, engages early TMDs of multipass proteins to promote their biogenesis by an unknown mechanism. Here, biochemical and structural analysis of intermediates during multipass protein biogenesis showed that the nascent chain is not engaged with Sec61, which is occluded and latched closed by CCDC47. Instead, Asterix binds to and redirects the substrate to a location behind Sec61, where the PAT complex contributes to a multipass translocon surrounding a semi-enclosed, lipid-filled cavity. Detection of multiple TMDs in this cavity after their emergence from the ribosome suggests that multipass proteins insert and fold behind Sec61. Accordingly, biogenesis of several multipass proteins was unimpeded by inhibitors of the Sec61 lateral gate. These findings elucidate the mechanism of an intramembrane chaperone and suggest a new framework for multipass membrane protein biogenesis at the endoplasmic reticulum.

PubMed: 36261528
DOI: 10.1038/s41586-022-05336-2

実験手法

ELECTRON MICROSCOPY (3.25 Å)