7tm3
Structure of the rabbit 80S ribosome stalled on a 2-TMD Rhodopsin intermediate in complex with the multipass transloconStructure of the rabbit 80S ribosome stalled on a 2-TMD Rhodopsin intermediate in complex with the multipass translocon
Structural highlights
FunctionRL8_RABIT Component of the large ribosomal subunit (PubMed:25601755, PubMed:26245381, PubMed:27863242, PubMed:30517857). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:25601755, PubMed:26245381, PubMed:27863242, PubMed:30517857).[1] [2] [3] [4] Publication Abstract from PubMedMultipass membrane proteins play numerous roles in biology and include receptors, transporters, ion channels and enzymes(1,2). How multipass proteins are co-translationally inserted and folded at the endoplasmic reticulum is not well understood(2). 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(3-9). The PAT complex, an intramembrane chaperone comprising Asterix and CCDC47, engages early TMDs of multipass proteins to promote their biogenesis by an unknown mechanism(10). 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(11). 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. Mechanism of an intramembrane chaperone for multipass membrane proteins.,Smalinskaite L, Kim MK, Lewis AJO, Keenan RJ, Hegde RS Nature. 2022 Nov;611(7934):161-166. doi: 10.1038/s41586-022-05336-2. Epub 2022 , Oct 19. PMID:36261528[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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