9WNO

Cryo-EM structure of Candida glabrata GPI mannosyltransferase I bound to Dol-P-Man

Summary for 9WNO

• Entry DOI: 10.2210/pdb9wno/pdb
• EMDB information: 66120
• Descriptor: GPI mannosyltransferase 1, Protein PBN1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: gt-c, gpi, mannosyltransferase, membrane protein
• Biological source: Nakaseomyces glabratus; More
• Total number of polymer chains: 2
• Total formula weight: 100657.24

Authors

Sun, H.,Wu, W.H.,Yan, Z.F. (deposition date: 2025-09-05, release date: 2025-12-03, Last modification date: 2025-12-10)

Primary citation

Sun, H.,Wu, W.,Li, X.,Deng, Y.,Huang, J.,Yin, M.,Yan, Z.
Structural Insights into the Glycosylphosphatidylinositol Mannosyltransferase I Complex from Candida glabrata .
J Fungi, 11:-, 2025

PubMed Abstract: 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.

PubMed: 41295199
DOI: 10.3390/jof11110819

Experimental method

ELECTRON MICROSCOPY (3.48 Å)