ArticleThe Journal of general physiology2003
A cysteine scan of the inner vestibule of cyclic nucleotide-gated channels reveals architecture and rearrangement of the pore.
Article in The Journal of general physiology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29 citing papers in PubMed, 42 citations in OpenAlex.
- Full opening of helix bundle crossing does not lead to NaK channel activation.The Journal of general physiology · 2022Article
- The conformational wave in capsaicin activation of transient receptor potential vanilloid 1 ion channel.Nature communications · 2018Article
- Structural insights into the mechanisms of CNBD channel function.The Journal of general physiology · 2018Review
- Congruent pattern of accessibility identifies minimal pore gate in a non-symmetric voltage-gated sodium channel.Nature communications · 2016Article
- HCN Channel C-Terminal Region Speeds Activation Rates Independently of Autoinhibition.The Journal of membrane biology · 2015Article
- Conformational rearrangements in the transmembrane domain of CNGA1 channels revealed by single-molecule force spectroscopy.Nature communications · 2015Article
- Structure, dynamics and implied gating mechanism of a human cyclic nucleotide-gated channel.PLoS computational biology · 2014Article
- Paxilline inhibits BK channels by an almost exclusively closed-channel block mechanism.The Journal of general physiology · 2014Article
- A ring of threonines in the inner vestibule of the pore of CNGA1 channels constitutes a binding site for permeating ions.The Journal of physiology · 2012Article
- Bacillus anthracis edema factor substrate specificity: evidence for new modes of action.Toxins · 2012Review
- Where's the gate? Gating in the deep pore of the BK(Ca) channel.The Journal of general physiology · 2011Article
- Gating in CNGA1 channels.Pflugers Archiv : European journal of physiology · 2010Review
- The gates of ion channels and enzymes.Trends in biochemical sciences · 2010Review
- Conformational rearrangements in the S6 domain and C-linker during gating in CNGA1 channels.European biophysics journal : EBJ · 2009Article
- Structural determinants of gating in the TRPV1 channel.Nature structural & molecular biology · 2009Article
- The evolutionarily conserved residue A653 plays a key role in HERG channel closing.The Journal of physiology · 2009Article
- The analysis of desensitizing CNGA1 channels reveals molecular interactions essential for normal gating.The Journal of general physiology · 2009Article
- hERG gating microdomains defined by S6 mutagenesis and molecular modeling.The Journal of general physiology · 2008Article
- A comparison of electrophysiological properties of the CNGA1, CNGA1tandem and CNGA1cys-free channels.European biophysics journal : EBJ · 2008Article
- C-terminal movement during gating in cyclic nucleotide-modulated channels.The Journal of biological chemistry · 2008Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
Cyclic nucleotide-gated (CNG) channels belong to the P-loop-containing family of ion channels that also includes KcsA, MthK, and Shaker channels. In this study, we investigated the structure and rearrangement of the CNGA1 channel pore using cysteine mutations and cysteine-specific modification. We constructed 16 mutant channels, each one containing a cysteine mutation at one of the positions between 384 and 399 in the S6 region of the pore. By measuring currents activated by saturating concentrations of the full agonist cGMP and the partial agonists cIMP and cAMP, we show that mutating S6 residues to cysteine caused both favorable and unfavorable changes in the free energy of channel opening. The time course of cysteine modification with 2-aminoethylmethane thiosulfonate hydrochloride (MTSEA) was complex. For many positions we observed decreases in current activated by cGMP and concomitant increases in current activated by cIMP and cAMP. A model where modification affected both gating and permeation successfully reproduced the complex time course of modification for most of the mutant channels. From the model fits to the time course of modification for each mutant channel, we quantified the following: (a) the bimolecular rate constant of modification in the open state, (b) the change in conductance, and (c) the change in the free energy of channel opening for modification of each cysteine. At many S6 cysteines, modification by MTSEA caused a decrease in conductance and a favorable change in the free energy of channel opening. Our results are interpreted within the structural framework of the known structures of KcsA and MthK. We conclude that: (a) MTSEA modification affects both gating and permeation, (b) the open configuration of the pore of CNGA1 channels is consistent with the structure of MthK, and (c) the modification of S6 residues disrupts the helical packing of the closed channel, making it easier for channels to open.
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