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Visualizing KcsA conformational changes upon ion binding by infrared spectroscopy and atomistic modeling.

ABSTRACT: The effect of ion binding in the selectivity filter of the potassium channel KcsA is investigated by combining amide I Fourier-transform infrared spectroscopy with structure-based spectral modeling. Experimental difference IR spectra between K(+)-bound KcsA and Na(+)-bound KcsA are in good qualitative agreement with spectra modeled from structural ensembles generated from molecular dynamics simulations. The molecular origins of the vibrational modes contributing to differences in these spectra are determined not only from structural differences in the selectivity filter but also from the pore helices surrounding this region. Furthermore, the coordination of K(+) or Na(+) to carbonyls in the selectivity filter effectively decouples the vibrations of those carbonyls from the rest of the protein, creating local probes of the electrostatic environment. The results suggest that it is necessary to include the influence of the surrounding helices in discussing selectivity and transport in KcsA and, on a more general level, that IR spectroscopy offers a nonperturbative route to studying the structure and dynamics of ion channels.

SUBMITTER: Stevenson P

PROVIDER: S-EPMC4428008 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Visualizing KcsA conformational changes upon ion binding by infrared spectroscopy and atomistic modeling.

Stevenson Paul P Götz Christoph C Baiz Carlos R CR Akerboom Jasper J Tokmakoff Andrei A Vaziri Alipasha A

The journal of physical chemistry. B 20150425 18

The effect of ion binding in the selectivity filter of the potassium channel KcsA is investigated by combining amide I Fourier-transform infrared spectroscopy with structure-based spectral modeling. Experimental difference IR spectra between K(+)-bound KcsA and Na(+)-bound KcsA are in good qualitative agreement with spectra modeled from structural ensembles generated from molecular dynamics simulations. The molecular origins of the vibrational modes contributing to differences in these spectra a ...[more]

PMID: 25861001

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Project description:Structure and dynamics of voltage-gated ion channels, in particular the motion of the S4 helix, is a highly interesting and hotly debated topic in current membrane protein research. It has critical implications for insertion and stabilization of membrane proteins as well as for finding how transitions occur in membrane proteins-not to mention numerous applications in drug design. Here, we present a full 1 micros atomic-detail molecular dynamics simulation of an integral Kv1.2 ion channel, comprising 120,000 atoms. By applying 0.052 V/nm of hyperpolarization, we observe structural rearrangements, including up to 120 degrees rotation of the S4 segment, changes in hydrogen-bonding patterns, but only low amounts of translation. A smaller rotation ( approximately 35 degrees ) of the extracellular end of all S4 segments is present also in a reference 0.5 micros simulation without applied field, which indicates that the crystal structure might be slightly different from the natural state of the voltage sensor. The conformation change upon hyperpolarization is closely coupled to an increase in 3(10) helix contents in S4, starting from the intracellular side. This could support a model for transition from the crystal structure where the hyperpolarization destabilizes S4-lipid hydrogen bonds, which leads to the helix rotating to keep the arginine side chains away from the hydrophobic phase, and the driving force for final relaxation by downward translation is partly entropic, which would explain the slow process. The coordinates of the transmembrane part of the simulated channel actually stay closer to the recently determined higher-resolution Kv1.2 chimera channel than the starting structure for the entire second half of the simulation (0.5-1 micros). Together with lipids binding in matching positions and significant thinning of the membrane also observed in experiments, this provides additional support for the predictive power of microsecond-scale membrane protein simulations.

Dataset Information

Visualizing KcsA conformational changes upon ion binding by infrared spectroscopy and atomistic modeling.

Publications

Visualizing KcsA conformational changes upon ion binding by infrared spectroscopy and atomistic modeling.

Similar Datasets

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