A TOG:αβ-Tubulin Complex Structure Reveals Conformation-Based Mechanisms for a Microtubule Polymerase

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dc.contributor.advisorYu, Hongtaoen
dc.contributor.committeeMemberAlbanesi, Joseph P.en
dc.contributor.committeeMemberRosen, Michael K.en
dc.contributor.committeeMemberRice, Luke M.en
dc.creatorAyaz, Pelin 1983-en
dc.date.accessioned2015-01-14T21:14:25Z
dc.date.available2015-01-14T21:14:25Z
dc.date.created2012-12
dc.date.issued2012-12-04
dc.date.submittedDecember 2012
dc.date.updated2015-01-14T21:13:50Z
dc.description.abstractStu2p/XMAP215/Dis1 family proteins are evolutionarily conserved regulatory factors that use alpha/beta-tubulin-interacting TOG (tumor overexpressed gene) domains to catalyze fast microtubule growth. Catalysis requires that these polymerases discriminate between unpolymerized and polymerized forms of alpha/beta-tubulin, but how they do so has remained unclear. In this study, we first introduce the polymerization blocked mutants of alpha/beta-tubulins that we developed as unique tools for biochemical studies of alpha/beta-tubulins to avoid the difficulties that has arisen from the self-assembly tendency of tubulins, then we report the structure of the TOG1 domain from Stu2p bound to the plus end polymerization blocked yeast alpha/beta-tubulin we created to facilitate crystallization. Our structure and further biochemical characterizations of the TOG1:alpha/beta-tubulin complex showed that TOG1 binds alpha/beta-tubulin in a way that excludes equivalent binding of a second TOG domain. Furthermore, TOG1 preferentially binds a “curved” conformation of alpha/beta-tubulin that cannot be incorporated into microtubules, contacting α- and β-tubulin surfaces that do not participate in microtubule assembly. Conformation-selective interactions with alpha/beta-tubulin explain how TOG-containing polymerases discriminate between unpolymerized and polymerized forms of alpha/beta-tubulin, and how they selectively recognize the growing end of the microtubule.en
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc900281614
dc.identifier.urihttps://hdl.handle.net/2152.5/ETD-UTSWMED-2012-12-60
dc.identifier.urihttps://hdl.handle.net/2152.5/1474
dc.language.isoenen
dc.subjectMicrotubule-Associated Proteinsen
dc.subjectMicrotubulesen
dc.subjectSaccharomyces cerevisiae Proteinsen
dc.subjectTubulinen
dc.titleA TOG:αβ-Tubulin Complex Structure Reveals Conformation-Based Mechanisms for a Microtubule Polymeraseen
dc.title.alternativeA TOG:[alpha][beta]-tubulin complex structure reveals conformation-based mechanisms for a microtubule polymeraseen
dc.typeThesisen
dc.type.materialTexten
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineMolecular Biophysicsen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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