Structural Insights into Ion Selectivity and Calcium Blockage in Cyclic Nucleotide Gated Channels
| dc.contributor.advisor | Jiang, Youxing | en |
| dc.creator | Derebe, Mehabaw Getahun | en |
| dc.date.accessioned | 2010-07-12T18:56:12Z | en |
| dc.date.accessioned | 2014-02-19T22:02:26Z | |
| dc.date.available | 2010-07-12T18:56:12Z | en |
| dc.date.available | 2014-02-19T22:02:26Z | |
| dc.date.issued | 2010-07-12T18:56:12Z | en |
| dc.description.abstract | Cyclic 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.identifier.other | 795781252 | en |
| dc.identifier.uri | http://hdl.handle.net/2152.5/727 | en |
| dc.language.iso | en | en |
| dc.subject.mesh | Ion Channel Gating | en |
| dc.subject.mesh | Sensory Functions | en |
| dc.subject.mesh | Recombinant Proteins | en |
| dc.title | Structural Insights into Ion Selectivity and Calcium Blockage in Cyclic Nucleotide Gated Channels | en |
| thesis.date.available | 2012-05-14 | en |
| thesis.degree.discipline | Molecular Biophysics | en |
| thesis.degree.grantor | Graduate School of Biomedical Sciences | en |
| thesis.degree.level | Ph.D. | en |
| thesis.degree.name | Doctor of Philosophy | en |