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Intramolecular Inhibition of the Ptb Domain in the Aida1 Neuronal Scaffolding Protein

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dc.contributor.advisorDonaldso, Logan
dc.contributor.authorChakkal, Tanvir Kaur
dc.date.accessioned2023-12-08T14:29:32Z
dc.date.available2023-12-08T14:29:32Z
dc.date.issued2023-12-08
dc.date.updated2023-12-08T14:29:31Z
dc.degree.disciplineBiology
dc.degree.levelMaster's
dc.degree.nameMSc - Master of Science
dc.description.abstractScaffolding proteins serve key functions in signalling cascades through mediating protein-protein interactions. A prominent member of the neuronal post-synaptic density is AIDA1, which is known to bind amyloid precursor protein (APP), a contributor to Alzheimer’s Disease (AD) development. Among the isoforms of AIDA1, AIDA1b is the largest and is unique in that its phosphotyrosine binding (PTB) domain is autoinhibited; thus, it cannot bind APP until this inhibition is relieved. This thesis presents structural and functional studies on AIDA1b. Fluorescence anisotropy and biolayer interferometry assays confirmed that the deletion of Exon 14 relieves the autoinhibition of the PTB domain, allowing AIDA1b to bind APP. However, Exon 14’s removal does not significantly impact the thermostability of AIDA1b. Moreover, Exon 14 contributes an alpha helical structural, with 3D bead models exhibiting potential domain reorganization upon Exon 14’s removal. The predicted structure of Exon 14 is an amphipathic alpha helix that presumably contacts the PTB domain in cooperation with other intervening sequences. Overall, AIDA1b can play a potential role in AD pathogenesis, with potential for contribution to novel therapeutic development.
dc.identifier.urihttps://hdl.handle.net/10315/41647
dc.languageen
dc.rightsAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.
dc.subjectBiochemistry
dc.subjectBiology
dc.subject.keywordsBiochemistry
dc.subject.keywordsStructural biology
dc.subject.keywordsMolecular neuroscience
dc.titleIntramolecular Inhibition of the Ptb Domain in the Aida1 Neuronal Scaffolding Protein
dc.typeElectronic Thesis or Dissertation

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