Structural Insights into the Glycosylphosphatidylinositol Mannosyltransferase I Complex from <i>Candida glabrata</i>.

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 Candida glabrata 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 defi

SUBMITTER: Sun H 

PROVIDER: S-EPMC12653191 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature