8imx

Cryo-EM structure of GPI-T with a chimeric GPI-anchored protein

spinqualitylabelsall models 8imx, resolution 2.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8imx is a 7 chain structure with sequence from Clavularia sp., Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.85Å Ligands: 05E, 6OU, 80T, 80Y, 81Q, AJP, CA, LBN, MG, NAG, PA1, Y01 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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 autoinhibitory loop into crucial catalytic cleft elements. Enzyme-proprotein binding in the transmembrane and luminal domains respectively powers the conformational rearrangement and induces a competent cleft. GPI-T thus integrates various weak specificity regions to form strong selectivity and prevent accidental activation. These findings provide important mechanistic insights into GPI-anchored protein biogenesis. Structures of liganded glycosylphosphatidylinositol transamidase illuminate GPI-AP biogenesis.,Xu Y, Li T, Zhou Z, Hong J, Chao Y, Zhu Z, Zhang Y, Qu Q, Li D Nat Commun. 2023 Sep 8;14(1):5520. doi: 10.1038/s41467-023-41281-y. PMID:37684232 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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