Structures of liganded glycosylphosphatidylinositol transamidase illuminate GPI-AP biogenesis.

ABSTRACT: Many eukaryotic receptors and enzymes rely on glycosylphosphatidylinositol (GPI) anchors for membrane localization and function. The transmembrane complex GPI-T recognizes diverse proproteins at a signal peptide region that lacks consensus sequence and replaces it with GPI via a transamidation reaction. How GPI-T maintains broad specificity while preventing unintentional cleavage is unclear. Here, substrates- and products-bound human GPI-T structures identify subsite features that enable broad proprotein specificity, inform catalytic mechanism, and reveal a multilevel safeguard mechanism against its promiscuity. In the absence of proproteins, the catalytic site is invaded by a locally stabilized loop. Activation requires energetically unfavorable rearrangements that transform the autoinhib

SUBMITTER: Xu Y 

PROVIDER: S-EPMC10491789 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature