The atomic structure of a eukaryotic oligosaccharyltransferase complex

Nature. 2018 Mar 15;555(7696):328-333. doi: 10.1038/nature25755. Epub 2018 Jan 22.

Abstract

N-glycosylation is a ubiquitous modification of eukaryotic secretory and membrane-bound proteins; about 90% of glycoproteins are N-glycosylated. The reaction is catalysed by an eight-protein oligosaccharyltransferase (OST) complex that is embedded in the endoplasmic reticulum membrane. Our understanding of eukaryotic protein N-glycosylation has been limited owing to the lack of high-resolution structures. Here we report a 3.5 Å resolution cryo-electron microscopy structure of the Saccharomyces cerevisiae OST complex, revealing the structures of subunits Ost1-Ost5, Stt3, Wbp1 and Swp1. We found that seven phospholipids mediate many of the inter-subunit interactions, and an Stt3 N-glycan mediates interactions with Wbp1 and Swp1 in the lumen. Ost3 was found to mediate the OST-Sec61 translocon interface, funnelling the acceptor peptide towards the OST catalytic site as the nascent peptide emerges from the translocon. The structure provides insights into co-translational protein N-glycosylation, and may facilitate the development of small-molecule inhibitors that target this process.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation
  • Biocatalysis
  • Catalytic Domain
  • Cryoelectron Microscopy*
  • Glycosylation
  • Hexosyltransferases / chemistry*
  • Hexosyltransferases / metabolism
  • Hexosyltransferases / ultrastructure*
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism
  • Membrane Proteins / ultrastructure*
  • Models, Molecular
  • Phospholipids / metabolism
  • Protein Subunits / chemistry
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / ultrastructure*

Substances

  • Membrane Proteins
  • Phospholipids
  • Protein Subunits
  • Saccharomyces cerevisiae Proteins
  • Hexosyltransferases
  • STT3 protein, S cerevisiae
  • dolichyl-diphosphooligosaccharide - protein glycotransferase