8B6L

Subtomogram average of the human Sec61-TRAP-OSTA-translocon

8B6L の概要

• エントリーDOI: 10.2210/pdb8b6l/pdb
• EMDBエントリー: 15870
• 分子名称: Protein transport protein Sec61 subunit alpha isoform 1, Oligosaccharyltransferase complex subunit OSTC, Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit 4, ... (16 entities in total)
• 機能のキーワード: membrane protein complex, protein translocation, n-glycosylation, signal peptide insertion, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 476567.94

構造登録者

Gemmer, M.,Fedry, J.M.M.,Forster, F.G. (登録日: 2022-09-27, 公開日: 2022-12-07, 最終更新日: 2024-11-20)

主引用文献

Gemmer, M.,Chaillet, M.L.,van Loenhout, J.,Cuevas Arenas, R.,Vismpas, D.,Grollers-Mulderij, M.,Koh, F.A.,Albanese, P.,Scheltema, R.A.,Howes, S.C.,Kotecha, A.,Fedry, J.,Forster, F.
Visualization of translation and protein biogenesis at the ER membrane.
Nature, 614:160-167, 2023

PubMed Abstract: The dynamic ribosome-translocon complex, which resides at the endoplasmic reticulum (ER) membrane, produces a major fraction of the human proteome. It governs the synthesis, translocation, membrane insertion, N-glycosylation, folding and disulfide-bond formation of nascent proteins. Although individual components of this machinery have been studied at high resolution in isolation, insights into their interplay in the native membrane remain limited. Here we use cryo-electron tomography, extensive classification and molecular modelling to capture snapshots of mRNA translation and protein maturation at the ER membrane at molecular resolution. We identify a highly abundant classical pre-translocation intermediate with eukaryotic elongation factor 1a (eEF1a) in an extended conformation, suggesting that eEF1a may remain associated with the ribosome after GTP hydrolysis during proofreading. At the ER membrane, distinct polysomes bind to different ER translocons specialized in the synthesis of proteins with signal peptides or multipass transmembrane proteins with the translocon-associated protein complex (TRAP) present in both. The near-complete atomic model of the most abundant ER translocon variant comprising the protein-conducting channel SEC61, TRAP and the oligosaccharyltransferase complex A (OSTA) reveals specific interactions of TRAP with other translocon components. We observe stoichiometric and sub-stoichiometric cofactors associated with OSTA, which are likely to include protein isomerases. In sum, we visualize ER-bound polysomes with their coordinated downstream machinery.

PubMed: 36697828
DOI: 10.1038/s41586-022-05638-5

実験手法

ELECTRON MICROSCOPY (7.6 Å)