{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/727"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/727","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"Structural Insights into Ion Selectivity and Calcium Blockage in Cyclic Nucleotide Gated Channels","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.","abstract_html":"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.","abstract_has_math":false,"creators":["Derebe, Mehabaw Getahun"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Jiang, Youxing"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-07-12T18:56:12Z","date_published":"2010-07-12T18:56:12Z","updated_at":"2026-07-24T05:52:31Z","subjects":["Ion Channel Gating","Sensory Functions","Recombinant Proteins"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["795781252"],"render_values":[{"text":"795781252","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/727","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Jiang, Youxing"]},{"key":"dc:creator","label":"Author","values":["Derebe, Mehabaw Getahun"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2010-07-12T18:56:12Z","2010-07-12"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","Text","dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Ion Channel Gating","Sensory Functions","Recombinant Proteins"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2152.5/727","795781252"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["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."]},{"key":"dc:format","label":"Dc Format","values":["Electronic","application/pdf","born digital"]},{"key":"dc:title","label":"Title","values":["Structural Insights into Ion Selectivity and Calcium Blockage in Cyclic Nucleotide Gated Channels"]}]}],"canonical_facts":{"dc:contributor":["Jiang, Youxing"],"dc:creator":["Derebe, Mehabaw Getahun"],"dc:date":["2010-07-12T18:56:12Z","2010-07-12"],"dc:description":["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."],"dc:format":["Electronic","application/pdf","born digital"],"dc:identifier":["https://hdl.handle.net/2152.5/727","795781252"],"dc:language":["en"],"dc:subject":["Ion Channel Gating","Sensory Functions","Recombinant Proteins"],"dc:title":["Structural Insights into Ion Selectivity and Calcium Blockage in Cyclic Nucleotide Gated Channels"],"dc:type":["Thesis","Text","dissertation"]},"updated_at":"2026-07-24T05:52:31Z"}