Structure of the eukaryotic protein O-mannosyltransferase Pmt1-Pmt2 complex

Nat Struct Mol Biol. 2019 Aug;26(8):704-711. doi: 10.1038/s41594-019-0262-6. Epub 2019 Jul 8.


In eukaryotes, a nascent peptide entering the endoplasmic reticulum (ER) is scanned by two Sec61 translocon-associated large membrane machines for protein N-glycosylation and protein O-mannosylation, respectively. While the structure of the eight-protein oligosaccharyltransferase complex has been determined recently, the structures of mannosyltransferases of the PMT family, which are an integral part of ER protein homeostasis, are still unknown. Here we report cryo-EM structures of the Saccharomyces cerevisiae Pmt1-Pmt2 complex bound to a donor and an acceptor peptide at 3.2-Å resolution, showing that each subunit contains 11 transmembrane helices and a lumenal β-trefoil fold termed the MIR domain. The structures reveal the substrate recognition model and confirm an inverting mannosyl-transferring reaction mechanism by the enzyme complex. Furthermore, we found that the transmembrane domains of Pmt1 and Pmt2 share a structural fold with the catalytic subunits of oligosaccharyltransferases, confirming a previously proposed evolutionary relationship between protein O-mannosylation and protein N-glycosylation.

Publication types

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

MeSH terms

  • Cryoelectron Microscopy
  • Glycosylation
  • Humans
  • Image Processing, Computer-Assisted
  • Mannose / metabolism
  • Mannosyltransferases / chemistry
  • Mannosyltransferases / genetics
  • Mannosyltransferases / metabolism
  • Mannosyltransferases / ultrastructure*
  • Models, Molecular
  • Multienzyme Complexes / chemistry
  • Multienzyme Complexes / metabolism
  • Multienzyme Complexes / ultrastructure*
  • Protein Conformation
  • Protein Domains
  • Protein Folding
  • Protein Processing, Post-Translational
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / ultrastructure*
  • Species Specificity
  • Substrate Specificity
  • Walker-Warburg Syndrome / genetics


  • Multienzyme Complexes
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • Mannosyltransferases
  • protein O-mannosyltransferase
  • Mannose