Dynamic Scaffolding in a G-Protein Signaling Cascade

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dc.contributor.advisorRanganathan, Ramaen
dc.creatorMishra, Prashanten
dc.date.accessioned2010-07-12T17:44:03Z
dc.date.available2010-07-12T17:44:03Z
dc.date.issued2009-06-18
dc.descriptionThe file named "mishraprashant.pdf" is the primary dissertation file. Supplemental movie files ("Mishra_Movie_S1.mpg", "Mishra_Movie_S2.mpg") are also available.en
dc.description.abstractThe InaD scaffold organizes a multi-protein complex that is essential for proper visual signaling in Drosophila photoreceptor cells. Here we show that one of the InaD PDZ domains (PDZ5) exists in a redox-dependent equilibrium between two conformations- a reduced form which is similar to the structure of other PDZ domains, and an oxidized form in which the ligand-binding site is distorted through formation of a strong intramolecular disulfide bond. We demonstrate transient light-dependent formation of this disulfide bond in vivo, and find that transgenic flies expressing a mutant InaD in which PDZ5 is locked in the reduced state display severe defects in termination of visual responses and visually-mediated reflex behavior. These studies demonstrate a novel conformational switch mechanism for PDZ domain function and suggest that InaD behaves more like a dynamic machine rather than a passive scaffold, regulating signal transduction at the millisecond timescale through cycles of conformational change.en
dc.format.digitalOriginborn digitalen
dc.format.mediumElectronicen
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc754633796
dc.identifier.urihttps://hdl.handle.net/2152.5/356
dc.language.isoenen
dc.subjectPDZ Domainsen
dc.subjectGTP-Binding Proteinsen
dc.subjectDrosophila Proteinsen
dc.titleDynamic Scaffolding in a G-Protein Signaling Cascadeen
dc.typeThesisen
dc.type.genredissertationen
dc.type.materialTexten
thesis.date.available2009-06-18
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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