1. Academic Validation
  2. Cryo-electron microscopy structures of human oligosaccharyltransferase complexes OST-A and OST-B

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.
Ana S Ramírez # 1 Julia Kowal # 1 Kaspar P Locher 2
Affiliations

Affiliations

  • 1 Institute of Molecular Biology and Biophysics, Eidgenössische Technische Hochschule (ETH), CH-8093 Zürich, Switzerland.
  • 2 Institute of Molecular Biology and Biophysics, Eidgenössische Technische Hochschule (ETH), CH-8093 Zürich, Switzerland. locher@mol.biol.ethz.ch.
  • # Contributed equally.
Abstract

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.

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