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6p25

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Structure of S. cerevisiae protein O-mannosyltransferase Pmt1-Pmt2 complex bound to the sugar donor and a peptide acceptor

6p25, resolution 3.20Å

Structural highlights

6p25 is a 3 chain structure with sequence from Saccharomyces cerevisiae W303. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.2Å
Ligands:
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PMT1_YEAST Protein O-mannosyltransferase involved in O-glycosylation which is essential for cell wall rigidity. Forms a heterodimeric complex with PMT2 and more rarely with PMT3 to transfer mannose from Dol-P-mannose to Ser or Thr residues on proteins. The PMT1-PMT2 complex participates in oxidative protein folding, ER-associated protein degradation (ERAD), as well as ER export. Required for incorporation of proteins in the cell wall.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

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-A resolution, showing that each subunit contains 11 transmembrane helices and a lumenal beta-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.

Structure of the eukaryotic protein O-mannosyltransferase Pmt1-Pmt2 complex.,Bai L, Kovach A, You Q, Kenny A, Li H Nat Struct Mol Biol. 2019 Jul 8. pii: 10.1038/s41594-019-0262-6. doi:, 10.1038/s41594-019-0262-6. PMID:31285605^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Girrbach V, Zeller T, Priesmeier M, Strahl-Bolsinger S. Structure-function analysis of the dolichyl phosphate-mannose: protein O-mannosyltransferase ScPmt1p. J Biol Chem. 2000 Jun 23;275(25):19288-96. doi: 10.1074/jbc.M001771200. PMID:10764776 doi:http://dx.doi.org/10.1074/jbc.M001771200
↑ Hirayama H, Fujita M, Yoko-o T, Jigami Y. O-mannosylation is required for degradation of the endoplasmic reticulum-associated degradation substrate Gas1*p via the ubiquitin/proteasome pathway in Saccharomyces cerevisiae. J Biochem. 2008 Apr;143(4):555-67. doi: 10.1093/jb/mvm249. Epub 2008 Jan 7. PMID:18182384 doi:http://dx.doi.org/10.1093/jb/mvm249
↑ Strahl-Bolsinger S, Immervoll T, Deutzmann R, Tanner W. PMT1, the gene for a key enzyme of protein O-glycosylation in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8164-8. PMID:8367478
↑ Gentzsch M, Immervoll T, Tanner W. Protein O-glycosylation in Saccharomyces cerevisiae: the protein O-mannosyltransferases Pmt1p and Pmt2p function as heterodimer. FEBS Lett. 1995 Dec 18;377(2):128-30. doi: 10.1016/0014-5793(95)01324-5. PMID:8543034 doi:http://dx.doi.org/10.1016/0014-5793(95)01324-5
↑ Bourdineaud JP, van der Vaart JM, Donzeau M, de Sampaio G, Verrips CT, Lauquin GJ. Pmt1 mannosyl transferase is involved in cell wall incorporation of several proteins in Saccharomyces cerevisiae. Mol Microbiol. 1998 Jan;27(1):85-98. PMID:9466258
↑ Bai L, Kovach A, You Q, Kenny A, Li H. Structure of the eukaryotic protein O-mannosyltransferase Pmt1-Pmt2 complex. Nat Struct Mol Biol. 2019 Jul 8. pii: 10.1038/s41594-019-0262-6. doi:, 10.1038/s41594-019-0262-6. PMID:31285605 doi:http://dx.doi.org/10.1038/s41594-019-0262-6