7T92

Structure of the peroxisomal retro-translocon formed by a heterotrimeric ubiquitin ligase complex

7T92 の概要

• エントリーDOI: 10.2210/pdb7t92/pdb
• EMDBエントリー: 25750
• 分子名称: Peroxin-12, Peroxin-2, Peroxin-10, ... (8 entities in total)
• 機能のキーワード: peroxisome, retro-translocon, ubiquitin ligase, translocase
• 由来する生物種: Thermothelomyces thermophilus ATCC 42464; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 174131.29

構造登録者

Peiqiang, F.,Tom, R. (登録日: 2021-12-17, 公開日: 2022-07-06, 最終更新日: 2024-02-28)

主引用文献

Feng, P.,Wu, X.,Erramilli, S.K.,Paulo, J.A.,Knejski, P.,Gygi, S.P.,Kossiakoff, A.A.,Rapoport, T.A.
A peroxisomal ubiquitin ligase complex forms a retrotranslocation channel.
Nature, 607:374-380, 2022

PubMed Abstract: Peroxisomes are ubiquitous organelles that house various metabolic reactions and are essential for human health. Luminal peroxisomal proteins are imported from the cytosol by mobile receptors, which then recycle back to the cytosol by a poorly understood process. Recycling requires receptor modification by a membrane-embedded ubiquitin ligase complex comprising three RING finger domain-containing proteins (Pex2, Pex10 and Pex12). Here we report a cryo-electron microscopy structure of the ligase complex, which together with biochemical and in vivo experiments reveals its function as a retrotranslocation channel for peroxisomal import receptors. Each subunit of the complex contributes five transmembrane segments that co-assemble into an open channel. The three ring finger domains form a cytosolic tower, with ring finger 2 (RF2) positioned above the channel pore. We propose that the N terminus of a recycling receptor is inserted from the peroxisomal lumen into the pore and monoubiquitylated by RF2 to enable extraction into the cytosol. If recycling is compromised, receptors are polyubiquitylated by the concerted action of RF10 and RF12 and degraded. This polyubiquitylation pathway also maintains the homeostasis of other peroxisomal import factors. Our results clarify a crucial step during peroxisomal protein import and reveal why mutations in the ligase complex cause human disease.

PubMed: 35768507
DOI: 10.1038/s41586-022-04903-x

実験手法

ELECTRON MICROSCOPY (3.1 Å)