9FD1

Structure of the Chaetomium thermophilum Pmt4-MIR domain with bound ligands

This is a non-PDB format compatible entry.

Summary for 9FD1

• Entry DOI: 10.2210/pdb9fd1/pdb
• Descriptor: Dolichyl-phosphate-mannose--protein mannosyltransferase, 1,2-ETHANEDIOL, ACETATE ION, ... (5 entities in total)
• Functional Keywords: protein o-mannosylation, glycosylation, er luminal domain, b-trefoil, thermostability, ligand binding, processivity, peptide binding protein
• Biological source: Chaetomium
• Total number of polymer chains: 1
• Total formula weight: 25694.51

Authors

McDowell, M.A.,Wild, K.,Sinning, I. (deposition date: 2024-05-16, release date: 2025-11-26, Last modification date: 2026-01-21)

Primary citation

McDowell, M.A.,Wild, K.,Fiorentino, F.,Bausewein, D.,Metschies, A.,Chiapparino, A.,Hackmann, Y.,Bilsing, F.L.,Brenske, D.,Mortensen, S.,Wu, D.,Robinson, C.V.,Strahl, S.,Sinning, I.
Structural characterisation of the fungal Pmt4 homodimer.
Nat Commun, 16:11134-11134, 2025

PubMed Abstract: Protein O-mannosyltransferases (PMTs) are conserved endoplasmic reticulum membrane-embedded enzymes responsible for the transfer of mannose from dolichol phosphate-mannose (Dol-P-Man) to serine/threonine-rich protein substrates or unfolded proteins. PMTs from three subfamilies form obligate dimers with different substrate specificities and require the concerted action of their transmembrane domains (TMDs) and a luminal MIR domain for catalysis. Here, we present structures, native mass spectrometry, and structure-based mutagenesis of the fungal Pmt4 homodimer. The core fold of the TMDs and MIR domain is conserved with the Pmt1-Pmt2 heterodimer, indicating a shared catalytic mechanism. Distinct from Pmt4, the MIR domain interacts in cis with the TMDs of the same subunit and has a β-hairpin insertion required for O-mannosylation of substrates. We further identify a cytosolic binding site for substrate Dol-P-Man within the Pmt4 TMDs, which is conserved amongst PMTs and important for in vivo activity. Thus, we provide a framework to understand the substrate specificity and regulation of the Pmt4 homodimer.

PubMed: 41392315
DOI: 10.1038/s41467-025-67412-1

Experimental method

X-RAY DIFFRACTION (1.22 Å)