2022
SH3 domain regulation of RhoGAP activity: Crosstalk between p120RasGAP and DLC1 RhoGAP
Chau JE, Vish KJ, Boggon TJ, Stiegler AL. SH3 domain regulation of RhoGAP activity: Crosstalk between p120RasGAP and DLC1 RhoGAP. Nature Communications 2022, 13: 4788. PMID: 35970859, PMCID: PMC9378701, DOI: 10.1038/s41467-022-32541-4.Peer-Reviewed Original ResearchConceptsRhoGAP activitySH3 domainCatalytic arginine fingerIntrinsic GTPase activityRho family GTPasesLiver cancer 1GAP proteinsRhoGAP proteinArginine fingerCo-crystal structureRas GTPasesGAP activityRho proteinsCellular processesGTPase activityMolecular basisKey regulatorTumor suppressorP120RasGAPCell migrationProteinGTPasesRhoGAPCancer 1Binding sites
2020
The pseudoGTPase group of pseudoenzymes
Stiegler AL, Boggon TJ. The pseudoGTPase group of pseudoenzymes. The FEBS Journal 2020, 287: 4232-4245. PMID: 32893973, PMCID: PMC7544640, DOI: 10.1111/febs.15554.Peer-Reviewed Original ResearchConceptsSignal transductionAmino acid divergenceEnzymatic activityLeucine-rich repeat kinase 2Amino acid differencesP190RhoGAP proteinsRepeat kinase 2Membrane traffickingCellular rolesEnzyme foldImportant mechanistic componentSmall GTPasesTranscriptional controlCellular functionsGTPasesKinase 2PseudoenzymesAcid differencesEC numbersCell migrationFunctional roleMitochondrial activityProteinCargo transportMechanistic components
2019
Crystal structures of p120RasGAP N-terminal SH2 domain in its apo form and in complex with a p190RhoGAP phosphotyrosine peptide
Chehayeb R, Stiegler AL, Boggon TJ. Crystal structures of p120RasGAP N-terminal SH2 domain in its apo form and in complex with a p190RhoGAP phosphotyrosine peptide. PLOS ONE 2019, 14: e0226113. PMID: 31891593, PMCID: PMC6938330, DOI: 10.1371/journal.pone.0226113.Peer-Reviewed Original ResearchConceptsN-terminal SH2 domainSH2 domainPhosphotyrosine peptidesNative gel shiftSite-directed mutagenesisGAP proteinsCo-crystal structurePhosphorylated tyrosineRas pathwayUnliganded formApo formCross-talk occursGel shiftP120RasGAPIsothermal titration calorimetryP190RhoGAPCell growthSpecific conformationCell proliferationProteinX-ray crystal structureTitration calorimetryDisease pathogenesisCrystal structureRho
2018
PseudoGTPase domains in p190RhoGAP proteins: a mini-review.
Stiegler AL, Boggon TJ. PseudoGTPase domains in p190RhoGAP proteins: a mini-review. Biochemical Society Transactions 2018, 46: 1713-1720. PMID: 30514771, PMCID: PMC6501215, DOI: 10.1042/bst20180481.Peer-Reviewed Original ResearchConceptsP190RhoGAP proteinsDetectable catalytic activityAbundant GTPaseSmall GTPasesRho familyStructural biologyCatalytic cleftEnzyme classesNew family membersFamily membersNoncanonical residuesGTPase enzymeKey regulatorCell migrationOverall proteinProteinBiochemical analysisGTPaseRecent discoveryRecent studiesDomainPseudoenzymesGTPasesCytokinesisDiscoveryThe N-Terminal GTPase Domain of p190RhoGAP Proteins Is a PseudoGTPase
Stiegler AL, Boggon TJ. The N-Terminal GTPase Domain of p190RhoGAP Proteins Is a PseudoGTPase. Structure 2018, 26: 1451-1461.e4. PMID: 30174148, PMCID: PMC6249675, DOI: 10.1016/j.str.2018.07.015.Peer-Reviewed Original ResearchConceptsP190RhoGAP proteinsN-terminal GTPase domainProtein-protein interaction domainsNucleotide exchange factorsCanonical GTPaseGTPase domainKnown proteinsEffector proteinsExchange factorInteraction domainNucleotide bindingMutational analysisCritical regulatorGTP-MgGTPProteinBiochemical analysisImportant groupBindingDomainPseudoenzymesGTPase