# ResearchStructural characterisation of the fungal Pmt4 homodimer

**Source**: https://www.bio.uni-heidelberg.de/en/newsroom/structural-characterisation-of-the-fungal-pmt4-homodimer
**Parent**: https://www.bio.uni-heidelberg.de/en

# Research Structural characterisation of the fungal Pmt4 homodimer

## Insights into substrate specificity and regulation of Pmt4

Protein O-mannosylation is an evolutionarily conserved and essential post-translational modification. Protein-O-mannosyltransferases (PMTs) are ER membrane-embedded enzymes responsible for the transfer of mannose from dolichol phosphate-mannose (Dol-P-Man) to unfolded proteins or serine/threonine-rich protein substrates. In yeast, unfolded protein O-mannosylation (UPOM) is important for ER protein quality control, while in humans impairment of O-mannosylation leads to severe diseases.

Pmt4 provides a powerful model for understanding congenital muscular dystrophies in humans linked to reduced O-mannosylation of α-dystroglycan (αDG) by POMT1-POMT2, as Pmt4 mannosylates αDG-derived peptides and is catalytically impaired by the insertion of pathogenic POMT1 mutations. In a collaborative effort, the groups of Irmgard Sinning (BZH), Sabine Strahl (COS) and Carol Robinson (Oxford, UK) combined cryo-EM and X-ray structure determination, native mass spectrometry, and *in vivo* functional assays to obtain mechanistic insights into the fungal Pmt4 homodimer. Their work substantially advances the understanding of the substrate specificity and regulation of the Pmt4 homodimer.

- [link to the paper](https://www.nature.com/articles/s41467-025-67412-1)
- [link to AG Sinning](https://bzh.db-engine.de/group/21/irmgard%20sinning)
- [link to AG Strahl](https://www.cos.uni-heidelberg.de/en/research-groups/glycobiology)

Ribbon model of the fungal Pmt4 homodimer (ER membrane embedded part) with dolichol-phosphate (Dol-P) at the active site (towards the ER lumen, upper part) and Dol-P-mannose at the cytoplasmic site (lower part) | Sinning

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