title: Exposure of residues in the cyclic nucleotide-gated channel pore: P region structure and function in gating.
abstract: In voltage-gated ion channels and in the homologous cyclic nucleotide-gated (CNG) channels, the loop between the S5 and S6 transmembrane segments (P region) is thought to form the lining of the pore. To investigate the structure and the role in gating of the P region of the bovine retinal CNG channel, we determined the accessibility of 11 cysteine-substituted P region residues to small, charged sulfhydryl reagents applied to the inside and outside of membrane patches in the open and closed states of the channel. The results suggest that the P region forms a loop that extends toward the central axis of the channel, analogous to the L3 loop of bacterial porin channels. Furthermore, the P region, in addition to forming the ion selectivity filter, functions as the channel gate, the structure of which changes when the channel opens.
authors.affiliation: Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
authors.forename: Z P
authors.initials: ZP
authors.lastname: Sun
authors.forename: M H
authors.initials: MH
authors.lastname: Akabas
authors.forename: E H
authors.initials: EH
authors.lastname: Goulding
authors.forename: A
authors.initials: A
authors.lastname: Karlin
authors.forename: S A
authors.initials: SA
authors.lastname: Siegelbaum
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002463:Cell Membrane Permeability; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D054815:Cyclic Nucleotide-Gated Cation Channels; D003545:Cysteine / Q000737:chemistry; D005020:Ethyl Methanesulfonate / Q000031:analogs & derivatives / Q000494:pharmacology; D005136:Eye Proteins / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013439:Sulfhydryl Reagents / Q000494:pharmacology
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; D005136:Eye Proteins; D007473:Ion Channels; D011993:Recombinant Fusion Proteins; D013439:Sulfhydryl Reagents; C093171:methanethiosulfonate ethylammonium; D005020:Ethyl Methanesulfonate; D003545:Cysteine