Titus Boggon, PhD
Associate Professor of Pharmacology and of Molecular Biophysics and BiochemistryCards
About
Research
Publications
2025
Cancer hotspot mutations rewire ERK2 specificity by selective exclusion of docking interactions
Torres Robles J, Stiegler A, Boggon T, Turk B. Cancer hotspot mutations rewire ERK2 specificity by selective exclusion of docking interactions. Journal Of Biological Chemistry 2025, 301: 108348. PMID: 40015635, DOI: 10.1016/j.jbc.2025.108348.Peer-Reviewed Original ResearchShort linear motifsCancer hotspot mutationsLinear motifsERK substratesYeast two-hybrid libraryHotspot mutationsTwo-hybrid libraryCancer-associated mutantsDocking interactionsWild-type ERK2Cancer-associated mutationsDocking motifBinding sequenceKinase ERK2Co-crystal structureMutant formsERK2 mutantsDisordered regionsERK2MotifStructural rationalePeptide bindingMutationsWT kinasePeptide fragmentsThe C2 domain augments Ras GTPase-activating protein catalytic activity
Paul M, Chen D, Vish K, Lartey N, Hughes E, Freeman Z, Saunders T, Stiegler A, King P, Boggon T. The C2 domain augments Ras GTPase-activating protein catalytic activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2418433122. PMID: 39899710, PMCID: PMC11831179, DOI: 10.1073/pnas.2418433122.Peer-Reviewed Original ResearchConceptsGTPase-activating proteinC2 domainActivity of GTPase-activating proteinGTPase-activating protein domainProtein catalytic activityDomain in vitroAllosteric lobeRas GTPasesSequence conservationGTPase activityAlphaFold modelsRasGAPSignaling defectsRasMutationsCatalytic activityConstitutive disruptionCatalytic advantageGTPaseAlphaFoldDomainGenesSynGAPProteinSequence
2024
Regulation and signaling of the LIM domain kinases
Casanova‐Sepúlveda G, Boggon T. Regulation and signaling of the LIM domain kinases. BioEssays 2024, 47: e2400184. PMID: 39361252, PMCID: PMC11663136, DOI: 10.1002/bies.202400184.Peer-Reviewed Original ResearchLIM domain kinaseDownstream of Rho GTPasesCofilin/actin depolymerizing factorActin cytoskeleton regulationIntra-molecular mechanismFilament severingDepolymerizing factorRho GTPasesActin depolymerizationCytoskeleton regulationRegulation mechanismKinaseLIMProteinRegulationGTPaseLIMK2LIMK1ActinEnzymeHuman healthSignalDepolymerizationCascadeMechanism120 Treatable Acute Neuroinflammatory Disease Associated with Complement Factor I Loss-of-function in the Plain Community
Reid W, Carson V, Krieger P, Stiegler A, Boggon T, Sullivan K, van den Heuvel L, Romberg N. 120 Treatable Acute Neuroinflammatory Disease Associated with Complement Factor I Loss-of-function in the Plain Community. Clinical Immunology 2024, 262: 110062. DOI: 10.1016/j.clim.2024.110062.Peer-Reviewed Original ResearchDistinct functional constraints driving conservation of the cofilin N-terminal regulatory tail
Sexton J, Potchernikov T, Bibeau J, Casanova-Sepúlveda G, Cao W, Lou H, Boggon T, De La Cruz E, Turk B. Distinct functional constraints driving conservation of the cofilin N-terminal regulatory tail. Nature Communications 2024, 15: 1426. PMID: 38365893, PMCID: PMC10873347, DOI: 10.1038/s41467-024-45878-9.Peer-Reviewed Original ResearchConceptsN-terminal regionActin bindingSequence requirementsLIM kinaseAnalysis of individual variantsInactivates cofilinS. cerevisiaeRegulatory tailFamily proteinsActin depolymerizationPhosphorylation sitesKinase recognitionSequence variantsInhibitory phosphorylationCofilinN-terminusIndividual variantsFunctional constraintsActinDisordered sequencesPhosphorylationSequenceBiochemical analysisSequence constraintsKinase
2023
Autoregulation of the LIM kinases by their PDZ domain
Casanova-Sepúlveda G, Sexton J, Turk B, Boggon T. Autoregulation of the LIM kinases by their PDZ domain. Nature Communications 2023, 14: 8441. PMID: 38114480, PMCID: PMC10730565, DOI: 10.1038/s41467-023-44148-4.Peer-Reviewed Original ResearchMutation 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 analysisPatientsCorrection: Rho family GTPase signaling through type II p21-activated kinases
Chetty A, Ha B, Boggon T. Correction: Rho family GTPase signaling through type II p21-activated kinases. Cellular And Molecular Life Sciences 2023, 80: 334. PMID: 37880444, PMCID: PMC11073300, DOI: 10.1007/s00018-023-04938-x.Peer-Reviewed Original ResearchStructure 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 ResearchConceptsSrc 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 studiesP120RasGAPAuthor Correction: Molecular basis for integrin adhesion receptor binding to p21-activated kinase 4 (PAK4)
Ha B, Yigit S, Natarajan N, Morse E, Calderwood D, Boggon T. Author Correction: Molecular basis for integrin adhesion receptor binding to p21-activated kinase 4 (PAK4). Communications Biology 2023, 6: 794. PMID: 37524913, PMCID: PMC10390574, DOI: 10.1038/s42003-023-05176-4.Peer-Reviewed Original Research
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Pharmacology
PO Box 208066, 333 Cedar Street
New Haven, CT 06520-8066
United States
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Sterling Hall of Medicine, B-Wing
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333 Cedar Street, Ste SHM B316A
New Haven, CT 06510
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New Haven, CT 06510