Functional implications of MIR domains in protein O-mannosylation
| Autor: | Yvonne Hackmann, Sabine Strahl, Gunter Stier, Klemens Wild, Sofia Mortensen, Antonija Grbavac, Irmgard Sinning, Andrea Schott, Ewa Zatorska, Antonella Chiapparino, Krishna Saxena, Harald Schwalbe, Hendrik R. A. Jonker |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Glycosylation
QH301-705.5 Science glycosyltransferase General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound Glycosyltransferase Biology (General) x-ray crystallography carbohydrate-binding module chemistry.chemical_classification Endoplasmic reticulum membrane General Immunology and Microbiology biology General Neuroscience General Medicine Nuclear magnetic resonance spectroscopy Processivity NMR Cell biology Enzyme chemistry Structural biology biology.protein protein O-mannosylation Medicine enzymatic processivity Carbohydrate-binding module |
| Zdroj: | eLife, Vol 9 (2020) 'eLife ', vol: 9, pages: e61189-1-e61189-23 (2020) |
| ISSN: | 2050-084X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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