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Title: Structure of the eukaryotic protein O-mannosyltransferase Pmt1–Pmt2 complex

Journal Article · · Nature Structural & Molecular Biology

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. In this paper 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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
National Institutes of Health (NIH); Michigan Economic Development Corporation and the Michigan Technology Tri-Corridor
OSTI ID:
1557293
Journal Information:
Nature Structural & Molecular Biology, Journal Name: Nature Structural & Molecular Biology Journal Issue: 8 Vol. 26; ISSN 1545-9993
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
ENGLISH

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  • Beltrán-Valero de Bernabé, Daniel; Currier, Sophie; Steinbrecher, Alice
  • The American Journal of Human Genetics, Vol. 71, Issue 5 https://doi.org/10.1086/342975
journal November 2002
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Uniparental disomy unveils a novel recessive mutation in POMT2 journal July 2018
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Cryo–electron microscopy structures of human oligosaccharyltransferase complexes OST-A and OST-B journal December 2019
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Membrane Topological Model of Glycosyltransferases of the GT-C Superfamily journal September 2019
Membrane Topological Model of Glycosyltransferases of the GT-C Superfamily journal September 2019
Cryo-EM Structures and Regulation of Arabinofuranosyltransferase AftD from Mycobacteria journal May 2020

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