ArticleProceedings of the National Academy of Sciences of the United States of America2013
Using protein backbone mutagenesis to dissect the link between ion occupancy and C-type inactivation in K+ channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Conformational Dynamic Studies of Prokaryotic Potassium Channels Explored by Homo-FRET Methodologies.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Article
- Structures of Gating Intermediates in a KJournal of molecular biology · 2021Article
- Tetraoctylammonium, a Long Chain Quaternary Ammonium Blocker, Promotes a Noncollapsed, Resting-Like Inactivated State in KcsA.International journal of molecular sciences · 2021Article
- Unraveling of a Strongly Correlated Dynamical Network of Residues Controlling the Permeation of Potassium in KcsA Ion Channel.Entropy (Basel, Switzerland) · 2021Article
- Selectivity filter ion binding affinity determines inactivation in a potassium channel.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- TOK channels use the two gates in classical KFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Multiscale Simulations of Biological Membranes: The Challenge To Understand Biological Phenomena in a Living Substance.Chemical reviews · 2019Article
- Conformational plasticity in the KcsA potassium channel pore helix revealed by homo-FRET studies.Scientific reports · 2019Article
- Rapid constriction of the selectivity filter underlies C-type inactivation in the KcsA potassium channel.The Journal of general physiology · 2018Article
- Single-particle cryo-EM structure of a voltage-activated potassium channel in lipid nanodiscs.eLife · 2018Article
- Chemical substitutions in the selectivity filter of potassium channels do not rule out constricted-like conformations for C-type inactivation.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Crystal structure of an inactivated mutant mammalian voltage-gated KNature structural & molecular biology · 2017Article
- Individual Ion Binding Sites in the K(+) Channel Play Distinct Roles in C-type Inactivation and in Recovery from Inactivation.Structure (London, England : 1993) · 2016Article
- Article
- Determinants of cation transport selectivity: Equilibrium binding and transport kinetics.The Journal of general physiology · 2015Review
- Chemical ligation of the influenza M2 protein for solid-state NMR characterization of the cytoplasmic domain.Protein science : a publication of the Protein Society · 2015Article
- Atom-by-atom engineering of voltage-gated ion channels: magnified insights into function and pharmacology.The Journal of physiology · 2015Review
- Ion channel engineering: perspectives and strategies.Journal of molecular biology · 2015Review
- Incorporation of Non-Canonical Amino Acids.Advances in experimental medicine and biology · 2015Review
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Authors and funding
4 authors at 1 institution in 1 country.
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Abstract
K(+) channels distinguish K(+) from Na(+) in the selectivity filter, which consists of four ion-binding sites (S1-S4, extracellular to intracellular) that are built mainly using the carbonyl oxygens from the protein backbone. In addition to ionic discrimination, the selectivity filter regulates the flow of ions across the membrane in a gating process referred to as C-type inactivation. A characteristic of C-type inactivation is a dependence on the permeant ion, but the mechanism by which permeant ions modulate C-type inactivation is not known. To investigate, we used amide-to-ester substitutions in the protein backbone of the selectivity filter to alter ion binding at specific sites and determined the effects on inactivation. The amide-to-ester substitutions in the protein backbone were introduced using protein semisynthesis or in vivo nonsense suppression approaches. We show that an ester substitution at the S1 site in the KcsA channel does not affect inactivation whereas ester substitutions at the S2 and S3 sites dramatically reduce inactivation. We determined the structure of the KcsA S2 ester mutant and found that the ester substitution eliminates K(+) binding at the S2 site. We also show that an ester substitution at the S2 site in the KvAP channel has a similar effect of slowing inactivation. Our results link C-type inactivation to ion occupancy at the S2 site. Furthermore, they suggest that the differences in inactivation of K(+) channels in K(+) compared with Rb(+) are due to different ion occupancies at the S2 site.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.