8b6l
From Proteopedia
Subtomogram average of the human Sec61-TRAP-OSTA-translocon
Structural highlights
DiseaseSC61B_HUMAN Loss-of-function SEC61B variations may cause autosomal dominant polycystic liver disease (PCLD) in patients that lack variations in known causative genes, such as PRKCSH and SEC63.[1] FunctionSC61B_HUMAN Component of SEC61 channel-forming translocon complex that mediates transport of signal peptide-containing precursor polypeptides across the endoplasmic reticulum (ER) (PubMed:12475939). Forms a ribosome receptor and a gated pore in the ER membrane, both functions required for cotranslational translocation of nascent polypeptides (PubMed:12475939). The SEC61 channel is also involved in ER membrane insertion of transmembrane proteins: it mediates membrane insertion of the first few transmembrane segments of proteins, while insertion of subsequent transmembrane regions of multi-pass membrane proteins is mediated by the multi-pass translocon (MPT) complex (PubMed:32820719, PubMed:36261522). The SEC61 channel cooperates with the translocating protein TRAM1 to import nascent proteins into the ER (PubMed:19121997).[2] [3] [4] [5] Publication Abstract from PubMedThe dynamic ribosome-translocon complex, which resides at the endoplasmic reticulum (ER) membrane, produces a major fraction of the human proteome(1,2). 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(3-7), 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. Visualization of translation and protein biogenesis at the ER membrane.,Gemmer M, Chaillet ML, van Loenhout J, Cuevas Arenas R, Vismpas D, Grollers-Mulderij M, Koh FA, Albanese P, Scheltema RA, Howes SC, Kotecha A, Fedry J, Forster F Nature. 2023 Feb;614(7946):160-167. doi: 10.1038/s41586-022-05638-5. Epub 2023 , Jan 25. PMID:36697828[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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