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Functional implications of MIR domains in protein O-mannosylation

Protein O-mannosyltransferases (PMTs) represent a conserved family of multispanning endoplasmic reticulum membrane proteins involved in glycosylation of S/T-rich protein substrates and unfolded proteins. PMTs work as dimers and contain a luminal MIR domain with a β-trefoil fold, which is susceptive...

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Hauptverfasser: Chiapparino, Antonella (VerfasserIn) , Grbavac, Antonija (VerfasserIn) , Jonker, Hendrik RA (VerfasserIn) , Hackmann, Yvonne (VerfasserIn) , Mortensen, Sofia (VerfasserIn) , Zatorska, Ewa (VerfasserIn) , Schott, Andrea (VerfasserIn) , Stier, Gunter (VerfasserIn) , Saxena, Krishna (VerfasserIn) , Wild, Klemens (VerfasserIn) , Schwalbe, Harald (VerfasserIn) , Strahl, Sabine (VerfasserIn) , Sinning, Irmgard (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 24 December 2020
In: eLife
Year: 2020, Jahrgang: 9, Pages: 1-23
ISSN:2050-084X
DOI:10.7554/eLife.61189
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.7554/eLife.61189
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Verfasserangaben:Antonella Chiapparino, Antonija Grbavac, Hendrik RA Jonker, Yvonne Hackmann, Sofia Mortensen, Ewa Zatorska, Andrea Schott, Gunter Stier, Krishna Saxena, Klemens Wild, Harald Schwalbe, Sabine Strahl, Irmgard Sinning
Beschreibung
Zusammenfassung:Protein O-mannosyltransferases (PMTs) represent a conserved family of multispanning endoplasmic reticulum membrane proteins involved in glycosylation of S/T-rich protein substrates and unfolded proteins. PMTs work as dimers and contain a luminal MIR domain with a β-trefoil fold, which is susceptive for missense mutations causing α-dystroglycanopathies in humans. Here, we analyze PMT-MIR domains by an integrated structural biology approach using X-ray crystallography and NMR spectroscopy and evaluate their role in PMT function in vivo. We determine Pmt2- and Pmt3-MIR domain structures and identify two conserved mannose-binding sites, which are consistent with general β-trefoil carbohydrate-binding sites (α, β), and also a unique PMT2-subfamily exposed FKR motif. We show that conserved residues in site α influence enzyme processivity of the Pmt1-Pmt2 heterodimer in vivo. Integration of the data into the context of a Pmt1-Pmt2 structure and comparison with homologous β-trefoil - carbohydrate complexes allows for a functional description of MIR domains in protein O-mannosylation.
Beschreibung:Gesehen am 17.02.2022
Beschreibung:Online Resource
ISSN:2050-084X
DOI:10.7554/eLife.61189

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