2023
Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations
Zhao S, Mekbib K, van der Ent M, Allington G, Prendergast A, Chau J, Smith H, Shohfi J, Ocken J, Duran D, Furey C, Hao L, Duy P, Reeves B, Zhang J, Nelson-Williams C, Chen D, Li B, Nottoli T, Bai S, Rolle M, Zeng X, Dong W, Fu P, Wang Y, Mane S, Piwowarczyk P, Fehnel K, See A, Iskandar B, Aagaard-Kienitz B, Moyer Q, Dennis E, Kiziltug E, Kundishora A, DeSpenza T, Greenberg A, Kidanemariam S, Hale A, Johnston J, Jackson E, Storm P, Lang S, Butler W, Carter B, Chapman P, Stapleton C, Patel A, Rodesch G, Smajda S, Berenstein A, Barak T, Erson-Omay E, Zhao H, Moreno-De-Luca A, Proctor M, Smith E, Orbach D, Alper S, Nicoli S, Boggon T, Lifton R, Gunel M, King P, Jin S, Kahle K. Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations. Nature Communications 2023, 14: 7452. PMID: 37978175, PMCID: PMC10656524, DOI: 10.1038/s41467-023-43062-z.Peer-Reviewed Original ResearchConceptsEphrin receptor B4Galen malformationBrain arteriovenous malformationsP120 RasGAPTransmitted variantsArteriovenous malformationsDe novo variantsSingle-cell transcriptomesSignificant burdenCerebrovascular developmentIntegrative genomic analysisEndothelial cellsVenous networkAdditional probandsMalformationsNovo variantsMissense variantsGenomic analysisDevelopmental angiogenesisVascular developmentDamaging variantsVeinRasGAPIntegrated analysisPatientsStructure Determination of SH2–Phosphopeptide Complexes by X-Ray Crystallography: The Example of p120RasGAP
Stiegler A, Boggon T. Structure Determination of SH2–Phosphopeptide Complexes by X-Ray Crystallography: The Example of p120RasGAP. Methods In Molecular Biology 2023, 2705: 77-89. PMID: 37668970, PMCID: PMC11059313, DOI: 10.1007/978-1-0716-3393-9_5.Peer-Reviewed Original ResearchMeSH KeywordsCrystallography, X-RayP120 GTPase Activating ProteinPhosphopeptidesPhosphotyrosineX-Ray DiffractionConceptsSrc homology 2SH2 domain bindsSH2 domainDomain bindsNew molecular-level insightsSH2 domain proteinsMolecular-level insightsX-ray crystallographyX-ray diffraction studiesDomain proteinsPartner proteinsHomology 2Three-dimensional structureMolecular detailsStructure determinationSuitable crystalsCanonical interactionsVapour-diffusion methodCareful structural analysisDrop vapor diffusion methodCrystallographic studiesCrystallography studiesSH2-phosphopeptide complexesDiffraction studiesP120RasGAPDiverse p120RasGAP interactions with doubly phosphorylated partners EphB4, p190RhoGAP, and Dok1
Vish K, Stiegler A, Boggon T. Diverse p120RasGAP interactions with doubly phosphorylated partners EphB4, p190RhoGAP, and Dok1. Journal Of Biological Chemistry 2023, 299: 105098. PMID: 37507023, PMCID: PMC10470053, DOI: 10.1016/j.jbc.2023.105098.Peer-Reviewed Original ResearchConceptsSH2 domainSpatial-temporal regulationDual SH2 domainsProper vascular developmentKey binding partnerProtein familySH2 interactionsBinding partnerHuman proteinsDistinct binding interactionsWeakened affinityVascular developmentRasGAPConformational differencesP190RhoGAPSmall-angle X-ray scatteringBindingBinding interactionsAffinity measurementsEphB4DomainGTPaseDok1X-ray scatteringProtein
2022
Tandem engagement of phosphotyrosines by the dual SH2 domains of p120RasGAP
Stiegler A, Vish K, Boggon T. Tandem engagement of phosphotyrosines by the dual SH2 domains of p120RasGAP. Structure 2022, 30: 1603-1614.e5. PMID: 36417908, PMCID: PMC9722645, DOI: 10.1016/j.str.2022.10.009.Peer-Reviewed Original ResearchMeSH KeywordsGTPase-Activating ProteinsP120 GTPase Activating ProteinPhosphotyrosineSrc Homology DomainsTyrosineConceptsGTPase-activating proteinsSH2 domainSH2-SH3Src homology 2 domainDual SH2 domainsPhosphotyrosine residuesSH3 domainRho GTPasesPhosphotyrosine recognitionTarget proteinsSynergistic bindingPhosphotyrosineP120RasGAPConformational flexibilityProteinSelectivity mechanismAffinity measurementsDomainGTPasesClose proximityCassetteCrystal structureResiduesCompact arrangementBinding