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

Abstract

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.

Authors:
ORCiD logo [1];  [1];  [1];  [1]; ORCiD logo [1]
  1. Van Andel Research Inst., Grand Rapids, MI (United States)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH); Michigan Economic Development Corporation and the Michigan Technology Tri-Corridor
OSTI Identifier:
1557293
Grant/Contract Number:  
R01 CA231466; 085P1000817
Resource Type:
Accepted Manuscript
Journal Name:
Nature Structural & Molecular Biology
Additional Journal Information:
Journal Volume: 26; Journal Issue: 8; Journal ID: ISSN 1545-9993
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; Cryoelectron microscopy; Glycobiology; Glycosylation; Transferases

Citation Formats

Bai, Lin, Kovach, Amanda, You, Qinglong, Kenny, Alanna, and Li, Huilin. Structure of the eukaryotic protein O-mannosyltransferase Pmt1–Pmt2 complex. United States: N. p., 2019. Web. https://doi.org/10.1038/s41594-019-0262-6.
Bai, Lin, Kovach, Amanda, You, Qinglong, Kenny, Alanna, & Li, Huilin. Structure of the eukaryotic protein O-mannosyltransferase Pmt1–Pmt2 complex. United States. https://doi.org/10.1038/s41594-019-0262-6
Bai, Lin, Kovach, Amanda, You, Qinglong, Kenny, Alanna, and Li, Huilin. Mon . "Structure of the eukaryotic protein O-mannosyltransferase Pmt1–Pmt2 complex". United States. https://doi.org/10.1038/s41594-019-0262-6. https://www.osti.gov/servlets/purl/1557293.
@article{osti_1557293,
title = {Structure of the eukaryotic protein O-mannosyltransferase Pmt1–Pmt2 complex},
author = {Bai, Lin and Kovach, Amanda and You, Qinglong and Kenny, Alanna and Li, Huilin},
abstractNote = {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.},
doi = {10.1038/s41594-019-0262-6},
journal = {Nature Structural & Molecular Biology},
number = 8,
volume = 26,
place = {United States},
year = {2019},
month = {7}
}

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    Works referencing / citing this record:

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