ArticleThe Journal of biological chemistry2011
Analysis of membrane topology and identification of essential residues for the yeast endoplasmic reticulum inositol acyltransferase Gwt1p.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 36 citations in OpenAlex.
- Structural insights into the inhibition mechanism of fungal GWT1 by manogepix.Nature communications · 2024Article
- Topological and enzymatic analysis of human Alg2 mannosyltransferase reveals its role in lipid-linked oligosaccharide biosynthetic pathway.Communications biology · 2022Article
- Novel Promising Antifungal Target Proteins for Conquering Invasive Fungal Infections.Frontiers in microbiology · 2022Review
- Enhanced Efflux Pump Expression inAntimicrobial agents and chemotherapy · 2020Article
- Biosynthesis and biology of mammalian GPI-anchored proteins.Open biology · 2020Review
- Hedgehog Acyltransferase Promotes Uptake of Palmitoyl-CoA across the Endoplasmic Reticulum Membrane.Cell reports · 2019Article
- Evaluation of Resistance Development to the Gwt1 Inhibitor Manogepix (APX001A) inAntimicrobial agents and chemotherapy · 2019Article
- Synthesis of analogs of the Gwt1 inhibitor manogepix (APX001A) and in vitro evaluation against Cryptococcus spp.Bioorganic & medicinal chemistry letters · 2019Article
- Function of a membrane-embedded domain evolutionarily multiplied in the GPI lipid anchor pathway proteins PIG-B, PIG-M, PIG-U, PIG-W, PIG-V, and PIG-Z.Cell cycle (Georgetown, Tex.) · 2018Article
- Chemical crosslinking and mass spectrometry to elucidate the topology of integral membrane proteins.PloS one · 2017Article
- Chemogenetic E-MAP in Saccharomyces cerevisiae for Identification of Membrane Transporters Operating Lipid Flip Flop.PLoS genetics · 2016Article
- Biosynthesis of GPI-anchored proteins: special emphasis on GPI lipid remodeling.Journal of lipid research · 2016Review
- Chemical Genomics-Based Antifungal Drug Discovery: Targeting Glycosylphosphatidylinositol (GPI) Precursor Biosynthesis.ACS infectious diseases · 2015Article
- Biosynthesis and deficiencies of glycosylphosphatidylinositol.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2014Review
- Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glycosylphosphatidylinositol (GPI) is a post-translational modification that anchors cell surface proteins to the plasma membrane, and GPI modifications occur in all eukaryotes. Biosynthesis of GPI starts on the cytoplasmic face of the endoplasmic reticulum (ER) membrane, and GPI precursors flip from the cytoplasmic side to the luminal side of the ER, where biosynthesis of GPI precursors is completed. Gwt1p and PIG-W are inositol acyltransferases that transfer fatty acyl chains to the inositol moiety of GPI precursors in yeast and mammalian cells, respectively. To ascertain whether flipping across the ER membrane occurs before or after inositol acylation of GPI precursors, we identified essential residues of PIG-W and Gwt1p and determined the membrane topology of Gwt1p. Guided by algorithm-based predictions of membrane topology, we experimentally identified 13 transmembrane domains in Gwt1p. We found that Gwt1p, PIG-W, and their orthologs shared four conserved regions and that these four regions in Gwt1p faced the luminal side of the ER membrane. Moreover, essential residues of Gwt1p and PIG-W faced the ER lumen or were near the luminal edge of transmembrane domains. The membrane topology of Gwt1p suggested that inositol acylation occurred on the luminal side of the ER membrane. Rather than stimulate flipping of the GPI precursor across the ER membrane, inositol acylation of GPI precursors may anchor the precursors to the luminal side of the ER membrane, preventing flip-flops.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.