Structural Insights into Ion Selectivity and Calcium Blockage in Cyclic Nucleotide Gated Channels

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dc.contributor.advisorJiang, Youxingen
dc.creatorDerebe, Mehabaw Getahunen
dc.date.accessioned2010-07-12T18:56:12Z
dc.date.available2010-07-12T18:56:12Z
dc.date.issued2010-07-12
dc.description.abstractCyclic nucleotides-gated (CNG) channels play an essential role in the visual and olfactory sensory systems and are ubiquitously expressed in a variety of neuronal and non neuronal cells. Details of their underlying ion selectivity properties are still not fully understood and a matter of debate in the absence of high resolution structures. Presented in this study are high resolution (1.58-1.95Å) crystal structures and functional analyses of engineered mimics of CNG channels by duplicating their selectivity filter sequences in the background of the bacterial non-selective NaK channel. Mimics share several striking functional similarities in ion selectivity with eukaryotic CNG channels: they are non-selective and permeate Na+ and K+ equally well; externally added Ca2+ serves as a permeating blocker, with the conserved acidic residue in the filter mediating Ca2+ binding. Structures reveal a hitherto unseen selectivity filter architecture that suggests that CNG channel selectivity filters likely comprise three contiguous ion binding sites. The high resolution structures also allow for a thorough characterization of monovalent and divalent ion permeation which, in combination with electrophysiological recordings, offers structural insight into CNG channel function at an unprecedented level of detail.en
dc.format.digitalOriginborn digitalen
dc.format.mediumElectronicen
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc795781252
dc.identifier.urihttps://hdl.handle.net/2152.5/727
dc.language.isoenen
dc.subjectIon Channel Gatingen
dc.subjectSensory Functionsen
dc.subjectRecombinant Proteinsen
dc.titleStructural Insights into Ion Selectivity and Calcium Blockage in Cyclic Nucleotide Gated Channelsen
dc.typeThesisen
dc.type.genredissertationen
dc.type.materialTexten
thesis.date.available2012-05-14
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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