Structural basis for coupling protein transport and N-glycosylation at the mammalian endoplasmic reticulum

Science. 2018 Apr 13;360(6385):215-219. doi: 10.1126/science.aar7899. Epub 2018 Mar 8.


Protein synthesis, transport, and N-glycosylation are coupled at the mammalian endoplasmic reticulum by complex formation of a ribosome, the Sec61 protein-conducting channel, and oligosaccharyltransferase (OST). Here we used different cryo-electron microscopy approaches to determine structures of native and solubilized ribosome-Sec61-OST complexes. A molecular model for the catalytic OST subunit STT3A (staurosporine and temperature sensitive 3A) revealed how it is integrated into the OST and how STT3-paralog specificity for translocon-associated OST is achieved. The OST subunit DC2 was placed at the interface between Sec61 and STT3A, where it acts as a versatile module for recruitment of STT3A-containing OST to the ribosome-Sec61 complex. This detailed structural view on the molecular architecture of the cotranslational machinery for N-glycosylation provides the basis for a mechanistic understanding of glycoprotein biogenesis at the endoplasmic reticulum.

Publication types

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

MeSH terms

  • Cryoelectron Microscopy
  • Endoplasmic Reticulum / metabolism*
  • Glycosylation
  • HEK293 Cells
  • Hexosyltransferases / chemistry*
  • Hexosyltransferases / ultrastructure
  • Humans
  • Membrane Proteins / chemistry*
  • Membrane Proteins / ultrastructure
  • Models, Molecular*
  • Protein Conformation
  • Protein Transport
  • Ribosomes / chemistry*
  • Ribosomes / ultrastructure
  • SEC Translocation Channels / chemistry*
  • SEC Translocation Channels / ultrastructure


  • Membrane Proteins
  • SEC Translocation Channels
  • Hexosyltransferases
  • STT3A protein, human
  • dolichyl-diphosphooligosaccharide - protein glycotransferase