Transmembrane Allosteric Coupling of the Gates in a Potassium Channel

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2013 Dec 18

PMID 24344306

Citations 55

Authors

Benjamin J Wylie

Manasi P Bhate

Ann E McDermott

Affiliations

Soon will be listed here.

Abstract

It has been hypothesized that transmembrane allostery is the basis for inactivation of the potassium channel KcsA: opening the intracellular gate is spontaneously followed by ion expulsion at the extracellular selectivity filter. This suggests a corollary: following ion expulsion at neutral pH, a spontaneous global conformation change of the transmembrane helices, similar to the motion involved in opening, is expected. Consequently, both the low potassium state and the low pH state of the system could provide useful models for the inactivated state. Unique NMR studies of full-length KcsA in hydrated bilayers provide strong evidence for such a mutual coupling across the bilayer: namely, upon removing ambient potassium ions, changes are seen in the NMR shifts of carboxylates E118 and E120 in the pH gate in the hinges of the inner transmembrane helix (98-103), and in the selectivity filter, all of which resemble changes seen upon acid-induced opening and inhibition and suggest that ion release can trigger channel helix opening.

Citing Articles

Selectivity filter mutations shift ion permeation mechanism in potassium channels.

Mironenko A, de Groot B, Kopec W PNAS Nexus. 2024; 3(7):pgae272.

PMID: 39015549 PMC: 11251424. DOI: 10.1093/pnasnexus/pgae272.

Anionic Phospholipids Shift the Conformational Equilibrium of the Selectivity Filter in the KcsA Channel to the Conductive Conformation: Predicted Consequences on Inactivation.

Renart M, Giudici A, Coll-Diez C, Gonzalez-Ros J, Poveda J Biomedicines. 2023; 11(5).

PMID: 37239046 PMC: 10216125. DOI: 10.3390/biomedicines11051376.

Mutational Insight into Allosteric Regulation of Kir Channel Activity.

Yekefallah M, Rasberry C, van Aalst E, Browning H, Amani R, Versteeg D ACS Omega. 2022; 7(48):43621-43634.

PMID: 36506180 PMC: 9730464. DOI: 10.1021/acsomega.2c04456.

Full opening of helix bundle crossing does not lead to NaK channel activation.

Kurauskas V, Tonelli M, Henzler-Wildman K J Gen Physiol. 2022; 154(12).

PMID: 36326620 PMC: 9640265. DOI: 10.1085/jgp.202213196.

High-Resolution Magic Angle Spinning NMR of KcsA in Liposomes: The Highly Mobile C-Terminus.

Howarth G, McDermott A Biomolecules. 2022; 12(8).

PMID: 36009016 PMC: 9405666. DOI: 10.3390/biom12081122.

References

Schneider R, Ader C, Lange A, Giller K, Hornig S, Pongs O . Solid-state NMR spectroscopy applied to a chimeric potassium channel in lipid bilayers. J Am Chem Soc. 2008; 130(23):7427-35. DOI: 10.1021/ja800190c. View

Tang X, Santarelli L, Heinemann S, Hoshi T . Metabolic regulation of potassium channels. Annu Rev Physiol. 2004; 66:131-59. DOI: 10.1146/annurev.physiol.66.041002.142720. View

Weingarth M, Prokofyev A, van der Cruijsen E, Nand D, Bonvin A, Pongs O . Structural determinants of specific lipid binding to potassium channels. J Am Chem Soc. 2013; 135(10):3983-8. DOI: 10.1021/ja3119114. View

Cordero-Morales J, Jogini V, Lewis A, Vasquez V, Cortes D, Roux B . Molecular driving forces determining potassium channel slow inactivation. Nat Struct Mol Biol. 2007; 14(11):1062-9. DOI: 10.1038/nsmb1309. View

Cuello L, Jogini V, Cortes D, Perozo E . Structural mechanism of C-type inactivation in K(+) channels. Nature. 2010; 466(7303):203-8. PMC: 3033749. DOI: 10.1038/nature09153. View

Cordero-Morales J, Cuello L, Zhao Y, Jogini V, Cortes D, Roux B . Molecular determinants of gating at the potassium-channel selectivity filter. Nat Struct Mol Biol. 2006; 13(4):311-8. DOI: 10.1038/nsmb1069. View

Jiang Y, Lee A, Chen J, Cadene M, Chait B, MacKinnon R . The open pore conformation of potassium channels. Nature. 2002; 417(6888):523-6. DOI: 10.1038/417523a. View

Ader C, Schneider R, Hornig S, Velisetty P, Wilson E, Lange A . A structural link between inactivation and block of a K+ channel. Nat Struct Mol Biol. 2008; 15(6):605-12. DOI: 10.1038/nsmb.1430. View

Lockless S, Zhou M, MacKinnon R . Structural and thermodynamic properties of selective ion binding in a K+ channel. PLoS Biol. 2007; 5(5):e121. PMC: 1858713. DOI: 10.1371/journal.pbio.0050121. View

10.

Lange A, Giller K, Hornig S, Martin-Eauclaire M, Pongs O, Becker S . Toxin-induced conformational changes in a potassium channel revealed by solid-state NMR. Nature. 2006; 440(7086):959-62. DOI: 10.1038/nature04649. View

11.

Yu L, Sun C, Song D, Shen J, Xu N, Gunasekera A . Nuclear magnetic resonance structural studies of a potassium channel-charybdotoxin complex. Biochemistry. 2005; 44(48):15834-41. DOI: 10.1021/bi051656d. View

12.

Cordero-Morales J, Jogini V, Chakrapani S, Perozo E . A multipoint hydrogen-bond network underlying KcsA C-type inactivation. Biophys J. 2011; 100(10):2387-93. PMC: 3093550. DOI: 10.1016/j.bpj.2011.01.073. View

13.

Uysal S, Cuello L, Cortes D, Koide S, Kossiakoff A, Perozo E . Mechanism of activation gating in the full-length KcsA K+ channel. Proc Natl Acad Sci U S A. 2011; 108(29):11896-9. PMC: 3141920. DOI: 10.1073/pnas.1105112108. View

14.

Zachariae U, Schneider R, Velisetty P, Lange A, Seeliger D, Wacker S . The molecular mechanism of toxin-induced conformational changes in a potassium channel: relation to C-type inactivation. Structure. 2008; 16(5):747-54. DOI: 10.1016/j.str.2008.01.018. View

15.

Imai S, Osawa M, Takeuchi K, Shimada I . Structural basis underlying the dual gate properties of KcsA. Proc Natl Acad Sci U S A. 2010; 107(14):6216-21. PMC: 2852003. DOI: 10.1073/pnas.0911270107. View

16.

Bhate M, McDermott A . Protonation state of E71 in KcsA and its role for channel collapse and inactivation. Proc Natl Acad Sci U S A. 2012; 109(38):15265-70. PMC: 3458351. DOI: 10.1073/pnas.1211900109. View

17.

Cornilescu G, Delaglio F, Bax A . Protein backbone angle restraints from searching a database for chemical shift and sequence homology. J Biomol NMR. 1999; 13(3):289-302. DOI: 10.1023/a:1008392405740. View

18.

McCoy J, Nimigean C . Structural correlates of selectivity and inactivation in potassium channels. Biochim Biophys Acta. 2011; 1818(2):272-85. PMC: 3253935. DOI: 10.1016/j.bbamem.2011.09.007. View

19.

Shen Y, Delaglio F, Cornilescu G, Bax A . TALOS+: a hybrid method for predicting protein backbone torsion angles from NMR chemical shifts. J Biomol NMR. 2009; 44(4):213-23. PMC: 2726990. DOI: 10.1007/s10858-009-9333-z. View

20.

Bhate M, Wylie B, Thompson A, Tian L, Nimigean C, McDermott A . Preparation of uniformly isotope labeled KcsA for solid state NMR: expression, purification, reconstitution into liposomes and functional assay. Protein Expr Purif. 2013; 91(2):119-24. PMC: 3805054. DOI: 10.1016/j.pep.2013.07.013. View