2024
Positive selection CRISPR screens reveal a druggable pocket in an oligosaccharyltransferase required for inflammatory signaling to NF-κB
Lampson B, Ramίrez A, Baro M, He L, Hegde M, Koduri V, Pfaff J, Hanna R, Kowal J, Shirole N, He Y, Doench J, Contessa J, Locher K, Kaelin W. Positive selection CRISPR screens reveal a druggable pocket in an oligosaccharyltransferase required for inflammatory signaling to NF-κB. Cell 2024, 187: 2209-2223.e16. PMID: 38670073, PMCID: PMC11149550, DOI: 10.1016/j.cell.2024.03.022.Peer-Reviewed Original ResearchConceptsWhole-genome CRISPR-Cas9 screenCRISPR-Cas9 screensCryoelectron microscopy studiesCell surface localizationLipopolysaccharide receptor Toll-like receptor 4OST complexToll-like receptor 4CRISPR screensNF-kBCatalytic subunitN-glycosylationActivate NF-kBBase editorsUncompetitive inhibition mechanismNGI-1Molecular mechanismsCatalytic siteLPS-treated cellsOligosaccharyltransferaseDruggable pocketSTT3AReceptor Toll-like receptor 4Drug mechanism of actionStructural studiesInflammatory signaling
2023
Signal recognition particle receptor-β (SR-β) coordinates cotranslational N-glycosylation
Phoomak C, Rinis N, Baro M, Shrimal S, Bennett D, Shaffer S, Lehrman M, Gilmore R, Contessa J. Signal recognition particle receptor-β (SR-β) coordinates cotranslational N-glycosylation. Science Advances 2023, 9: eade8079. PMID: 36921042, PMCID: PMC10017033, DOI: 10.1126/sciadv.ade8079.Peer-Reviewed Original ResearchConceptsSignal recognition particle receptorN-glycosylationProper protein foldingCotranslational N-glycosylationOligosaccharyltransferase complexPosttranslational modificationsProtein foldingSecretory compartmentsHigh-throughput screeningEndoplasmic reticulumCellular localizationUnrecognized functionChemical probesProteinTransloconReceptorsSubunitsFoldingReticulumMutationsPhenotypeCompartmentsAssemblyCellsLocalization