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TitleStructural Insights into the Glycosylphosphatidylinositol Mannosyltransferase I Complex from .
Journal, issue, pagesJ Fungi (Basel), Vol. 11, Issue 11, Year 2025
Publish dateNov 19, 2025
AuthorsHui Sun / Weihong Wu / Xiaomei Li / Yang Deng / Jiarong Huang / Meng Yin / Zhaofeng Yan /
PubMed AbstractThe global rise in resistance to first-line antifungal agents highlights the urgent need for new therapeutic strategies. Glycosylphosphatidylinositol (GPI)-anchored protein biosynthesis is an ...The global rise in resistance to first-line antifungal agents highlights the urgent need for new therapeutic strategies. Glycosylphosphatidylinositol (GPI)-anchored protein biosynthesis is an attractive target. The GPI mannosyltransferase I (GPI-MT-I), composed of Gpi14 and Pbn1, catalyzes the essential first mannose transfer from dolichol-phosphomannose (Dol-P-Man) to the GPI precursor. This initial mannosylation is critical for fungal cell wall integrity, yet the molecular basis of GPI-MT-I assembly and substrate recognition remains poorly understood. Here, we present the cryo-EM structure of GPI-MT-I in complex with Dol-P-Man, revealing how Gpi14 and Pbn1 form a stable complex and engage the mannose donor. An AlphaFold3-predicted acceptor-bound model further defines the structural basis of acceptor substrate recognition and suggests a plausible catalytic mechanism. Comparison with structural homologs highlights a distinct mode of substrate engagement by GPI-MT-I. Together, these findings establish a mechanistic framework for GPI-MT-I function with broader implications for the GPI-MT family.
External linksJ Fungi (Basel) / PubMed:41295199 / PubMed Central
MethodsEM (single particle)
Resolution3.48 Å
Structure data

66120

9wno

EMDB-66120, PDB-9wno:
Cryo-EM structure of Candida glabrata GPI mannosyltransferase I bound to Dol-P-Man
Method: EM (single particle) / Resolution: 3.48 Å

Chemicals

ChemComp-MJC:
dolichyl phosphate mannose

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • nakaseomyces glabratus (fungus)
KeywordsMEMBRANE PROTEIN / GT-C / GPI / Mannosyltransferase

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