Cryo-electron microscopy structures of human oligosaccharyltransferase complexes OST-A and OST-B

Science. 2019 Dec 13;366(6471):1372-1375. doi: 10.1126/science.aaz3505.


Oligosaccharyltransferase (OST) catalyzes the transfer of a high-mannose glycan onto secretory proteins in the endoplasmic reticulum. Mammals express two distinct OST complexes that act in a cotranslational (OST-A) or posttranslocational (OST-B) manner. Here, we present high-resolution cryo-electron microscopy structures of human OST-A and OST-B. Although they have similar overall architectures, structural differences in the catalytic subunits STT3A and STT3B facilitate contacts to distinct OST subunits, DC2 in OST-A and MAGT1 in OST-B. In OST-A, interactions with TMEM258 and STT3A allow ribophorin-I to form a four-helix bundle that can bind to a translating ribosome, whereas the equivalent region is disordered in OST-B. We observed an acceptor peptide and dolichylphosphate bound to STT3B, but only dolichylphosphate in STT3A, suggesting distinct affinities of the two OST complexes for protein substrates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cryoelectron Microscopy
  • Hexosyltransferases / chemistry*
  • Humans
  • Membrane Proteins / chemistry*
  • Protein Conformation
  • Protein Subunits / chemistry


  • Membrane Proteins
  • Protein Subunits
  • Hexosyltransferases
  • STT3A protein, human
  • STT3B protein, human
  • dolichyl-diphosphooligosaccharide - protein glycotransferase