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Cryo-EM structure of the yeast oligosaccharyltransferase (OST) complexCryo-EM structure of the yeast oligosaccharyltransferase (OST) complex
Structural highlights
FunctionOST1_YEAST Essential subunit of the N-oligosaccharyl transferase (OST) complex which catalyzes the transfer of a high mannose oligosaccharide from a lipid-linked oligosaccharide donor to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains. N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity. Publication Abstract from PubMedOligosaccharyltransferase (OST) is the central enzyme of N-linked protein glycosylation. It catalyzes the transfer of a pre-assembled glycan, GlcNAc(2)Man(9)Glc(3), from a dolichyl-pyrophosphate donor to acceptor sites in secretory proteins in the lumen of the endoplasmic reticulum. Precise recognition of the fully assembled glycan by OST is essential for the subsequent quality control steps of glycoprotein biosynthesis. However, the molecular basis of the OST-donor glycan interaction is unknown. Here we present cryo-EM structures of S. cerevisiae OST in distinct functional states. Our findings reveal that the terminal glucoses (Glc(3)) of a chemo-enzymatically generated donor glycan analog bind to a pocket formed by the non-catalytic subunits WBP1 and OST2. We further find that binding either donor or acceptor substrate leads to distinct primed states of OST, where subsequent binding of the other substrate triggers conformational changes required for catalysis. This alternate priming allows OST to efficiently process closely spaced N-glycosylation sites. Molecular basis for glycan recognition and reaction priming of eukaryotic oligosaccharyltransferase.,Ramirez AS, de Capitani M, Pesciullesi G, Kowal J, Bloch JS, Irobalieva RN, Reymond JL, Aebi M, Locher KP Nat Commun. 2022 Nov 26;13(1):7296. doi: 10.1038/s41467-022-35067-x. PMID:36435935[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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