Importance of lipid-pore loop interface for potassium channel structure and function
By Elwin A. W. van der Cruijsen, Deepak Nand, Markus Weingarth, Alexander Prokofyev, Sönke Hornig, Abhishek Arun Cukkemane, Alexandre M. J. J. Bonvin, Stefan Becker, Raymond E. Hulse, Eduardo Perozo, Olaf Pongs, and Marc Baldus.
Published in Proceedings of the National Academy of Sciences of the USA, 110(32):13008-13 on August 6, 2013. PMID: 23882077. PMCID: PMC3740848. Link to publication page.
Project: Dynamics of Ion Permeation and Conformational Coupling in – KcsA
Figure 1. SsNMR analysis of membrane-embedded Chim in the closed conductive state. (Left) Cartoon representation of the 3D ssNMR model of the closed state (residues Chim 22–115). Resolved CHHC restraints (highlighted in cyan) identified from the CHHC spectrum (250 µs and 500 µs 1H-1H mixing) that are unambiguous based on the KcsA crystal structure and the available chemical shifts are indicated by black dashed lines. Additional correlations unique for the ssNMR structure of Chim are shown by red dashed lines. (Right) Superposition of the Chim structural model (blue) and the KcsA crystal structure (gray) with three resolved ssNMR restraints confirming the extended α-helical turn for he chimeric channel along with their amino acid sequence comparison highlighting (orange) the 11 mutations distinguishing the turret region.
Abstract
Potassium (i.e., K+) channels allow for the controlled and selective passage of potassium ions across the plasma membrane via a conserved pore domain. In voltage-gated K+ channels, gating is the result of the coordinated action of two coupled gates: an activation gate at the intracellular entrance of the pore and an inactivation gate at the selectivity filter. By using solid-state NMR structural studies, in combination with electrophysiological experiments and molecular dynamics simulations, we show that the turret region connecting the outer transmembrane helix (transmembrane helix 1) and the pore helix behind the selectivity filter contributes to K+ channel inactivation and exhibits a remarkable structural plasticity that correlates to K+ channel inactivation. The transmembrane helix 1 unwinds when the K+ channel enters the inactivated state and rewinds during the transition to the closed state. In addition to well-characterized changes at the K+ ion coordination sites, this process is accompanied by conformational changes within the turret region and the pore helix. Further spectroscopic and computational results show that the same channel domain is critically involved in establishing functional contacts between pore domain and the cellular membrane. Taken together, our results suggest that the interaction between the K+ channel turret region and the lipid bilayer exerts an important influence on the selective passage of potassium ions via the K+ channel pore.
