2022
Autoinhibition of the GEF activity of cytoskeletal regulatory protein Trio is disrupted in neurodevelopmental disorder-related genetic variants
Bircher JE, Corcoran EE, Lam TT, Trnka MJ, Koleske AJ. Autoinhibition of the GEF activity of cytoskeletal regulatory protein Trio is disrupted in neurodevelopmental disorder-related genetic variants. Journal Of Biological Chemistry 2022, 298: 102361. PMID: 35963430, PMCID: PMC9467883, DOI: 10.1016/j.jbc.2022.102361.Peer-Reviewed Original ResearchConceptsSpectrin repeatsGEF1 domainPleckstrin homology regionExchange factor domainKey regulatory mechanismCytoskeletal regulatory proteinsSmall GTPase Rac1Autoinhibitory constraintsAccessory domainsNeurodevelopmental disordersGEF activityMultiple neurodevelopmental disordersKinase domainHomology regionProtein TrioGTPase Rac1Regulatory proteinsRegulatory mechanismsFactor domainSRS-6Genetic variantsGef1Disease variantsEnzymatic activityBio-Layer Interferometry
2020
Crystal structure of a guanine nucleotide exchange factor encoded by the scrub typhus pathogen Orientia tsutsugamushi
Lim C, Berk JM, Blaise A, Bircher J, Koleske AJ, Hochstrasser M, Xiong Y. Crystal structure of a guanine nucleotide exchange factor encoded by the scrub typhus pathogen Orientia tsutsugamushi. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 30380-30390. PMID: 33184172, PMCID: PMC7720168, DOI: 10.1073/pnas.2018163117.Peer-Reviewed Original ResearchConceptsBacterial GEFStructure-guided mutational analysisExchange factor domainRho family GTPasesObvious sequence similarityRho GTPases Rac1Pathogen Orientia tsutsugamushiAlters cell morphologyInteraction screenConvergent evolutionGEF domainHost interactorsExchange factorNucleotide displacementGEF activityCellular processesSequence similarityCytoskeletal structuresGTPases Rac1Ectopic expressionMutational analysisGEFRac1Factor domainPathogenic bacterium