NMR Studies of Lipid Regulation of the K Channel KcsA

Overview

Journal Biochim Biophys Acta Biomembr

Publisher Elsevier

Specialties Biochemistry
Biophysics
Cell Biology

Date 2020 Oct 16

PMID 33065136

Citations 4

Authors

Dongyu Zhang

Gary S Howarth

Lia A Parkin

Ann E McDermott

Affiliations

Soon will be listed here.

Abstract

The membrane environment, including specific lipid characteristics, plays important roles in the folding, stability, and gating of the prokaryotic potassium channel KcsA. Here we study the effect of membrane composition on the population of various functional states of KcsA. The spectra provide support for the previous observation of copurifying phospholipids with phosphoglycerol headgroups. Additional, exogenously added anionic lipids do not appear to be required to stabilize the open conductive conformation of KcsA, which was previously thought to be the case. On the contrary, NMR-based binding studies indicate that including anionic lipids in proteoliposomes at acidic pH leads to a weaker potassium ion affinity at the selectivity filter. Since K ion loss leads to channel inactivation, these results suggest that anionic lipids promote channel inactivation.

Citing Articles

Elucidating the role of lipid interactions in stabilizing the membrane protein KcsA.

Qiao P, Odenkirk M, Zheng W, Wang Y, Chen J, Xu W Biophys J. 2024; 123(18):3205-3216.

PMID: 39030907 PMC: 11427772. DOI: 10.1016/j.bpj.2024.07.019.

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.

From Bench to Biomolecular Simulation: Phospholipid Modulation of Potassium Channels.

Pipatpolkai T, Quetschlich D, Stansfeld P J Mol Biol. 2021; 433(17):167105.

PMID: 34139216 PMC: 8361781. DOI: 10.1016/j.jmb.2021.167105.

Informing NMR experiments with molecular dynamics simulations to characterize the dominant activated state of the KcsA ion channel.

Perez-Conesa S, Keeler E, Zhang D, Delemotte L, McDermott A J Chem Phys. 2021; 154(16):165102.

PMID: 33940802 PMC: 9250420. DOI: 10.1063/5.0040649.

References

Tucker S, Baukrowitz T . How highly charged anionic lipids bind and regulate ion channels. J Gen Physiol. 2008; 131(5):431-8. PMC: 2346576. DOI: 10.1085/jgp.200709936. View

Lundbaek J, Collingwood S, Ingolfsson H, Kapoor R, Andersen O . Lipid bilayer regulation of membrane protein function: gramicidin channels as molecular force probes. J R Soc Interface. 2009; 7(44):373-95. PMC: 2842803. DOI: 10.1098/rsif.2009.0443. View

Roux B . Ion conduction and selectivity in K(+) channels. Annu Rev Biophys Biomol Struct. 2005; 34:153-71. DOI: 10.1146/annurev.biophys.34.040204.144655. View

Molina M, Barrera F, Fernandez A, Poveda J, Renart M, Encinar J . Clustering and coupled gating modulate the activity in KcsA, a potassium channel model. J Biol Chem. 2006; 281(27):18837-48. DOI: 10.1074/jbc.M600342200. View

Guigas G, Weiss M . Effects of protein crowding on membrane systems. Biochim Biophys Acta. 2016; 1858(10):2441-2450. DOI: 10.1016/j.bbamem.2015.12.021. View

Zhou M, MacKinnon R . A mutant KcsA K(+) channel with altered conduction properties and selectivity filter ion distribution. J Mol Biol. 2004; 338(4):839-46. DOI: 10.1016/j.jmb.2004.03.020. View

Lenaeus M, Vamvouka M, Focia P, Gross A . Structural basis of TEA blockade in a model potassium channel. Nat Struct Mol Biol. 2005; 12(5):454-9. DOI: 10.1038/nsmb929. View

Mance D, Sinnige T, Kaplan M, Narasimhan S, Daniels M, Houben K . An Efficient Labelling Approach to Harness Backbone and Side-Chain Protons in (1) H-Detected Solid-State NMR Spectroscopy. Angew Chem Int Ed Engl. 2015; 54(52):15799-803. PMC: 4691318. DOI: 10.1002/anie.201509170. View

van Dalen A, Hegger S, Killian J, de Kruijff B . Influence of lipids on membrane assembly and stability of the potassium channel KcsA. FEBS Lett. 2002; 525(1-3):33-8. DOI: 10.1016/s0014-5793(02)03061-2. View

10.

BLIGH E, Dyer W . A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959; 37(8):911-7. DOI: 10.1139/o59-099. View

11.

Iwamoto M, Oiki S . Amphipathic antenna of an inward rectifier K+ channel responds to changes in the inner membrane leaflet. Proc Natl Acad Sci U S A. 2012; 110(2):749-54. PMC: 3545751. DOI: 10.1073/pnas.1217323110. View

12.

Lee W, Tonelli M, Markley J . NMRFAM-SPARKY: enhanced software for biomolecular NMR spectroscopy. Bioinformatics. 2014; 31(8):1325-7. PMC: 4393527. DOI: 10.1093/bioinformatics/btu830. View

13.

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

14.

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

15.

Heginbotham L, Miller C . Functional reconstitution of a prokaryotic K+ channel. J Gen Physiol. 1998; 111(6):741-9. PMC: 2217152. DOI: 10.1085/jgp.111.6.741. View

16.

Demmers J, van Dalen A, de Kruijff B, Heck A, Killian J . Interaction of the K+ channel KcsA with membrane phospholipids as studied by ESI mass spectrometry. FEBS Lett. 2003; 541(1-3):28-32. DOI: 10.1016/s0014-5793(03)00282-5. View

17.

Marius P, de Planque M, Williamson P . Probing the interaction of lipids with the non-annular binding sites of the potassium channel KcsA by magic-angle spinning NMR. Biochim Biophys Acta. 2011; 1818(1):90-6. PMC: 3236287. DOI: 10.1016/j.bbamem.2011.09.017. View

18.

van der Cruijsen E, Prokofyev A, Pongs O, Baldus M . Probing Conformational Changes during the Gating Cycle of a Potassium Channel in Lipid Bilayers. Biophys J. 2017; 112(1):99-108. PMC: 5232892. DOI: 10.1016/j.bpj.2016.12.001. View

19.

Raetz C, Dowhan W . Biosynthesis and function of phospholipids in Escherichia coli. J Biol Chem. 1990; 265(3):1235-8. View

20.

Bolivar J, East J, Marsh D, Lee A . Effects of lipid structure on the state of aggregation of potassium channel KcsA. Biochemistry. 2012; 51(30):6010-6. DOI: 10.1021/bi3006253. View