Conformational Changes and Gating at the Selectivity Filter of Potassium Channels

@article{citeulike:2946065, abstract = {Abstract: The translocation of ions and water across cell membranes is a prerequisite for many of lifes processes. K+ channels are a diverse family of integral membrane proteins through which K+ can pass selectively. There is an ongoing debate about the nature of conformational changes associated with the opening and closing and conductive and nonconductive states of potassium (K+) channels. These changes depend on the membrane potential, the K+ concentration gradient, and large scale motions of transmembrane helices and associated residues. Experiments also suggest that local structural changes in the selectivity filter may act as the dominant gate referred to as C-type inactivation. Herein we present an extensive computational study on KirBac, which supports the existence of a physical gate or constriction in the selectivity filter (SF) of K+ channels. Our computations identify a new selectivity filter structure, which is likely associated with C-type inactivation. Specifically, the four peptide chains that comprise the filter adopt an unusual structure in which their dihedrals alternate between left- and right-handed Ramachandran angles, which also justifies the need for conservation of glycine in the K+ selectivity filter, since it is the only residue able to play this bifunctional role.}, address = {Physical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, U.K., Center for Molecular Modelling and Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pensylvannia 19104-6323, and Department of Chemistry and Applied Biosciences, ETH Zurich, USI - Campus, via Giuseppe Buffi 13, 6900 Lugano, Switzerland}, author = {Domene, Carmen and Klein, Michael L. and Branduardi, Davide and Gervasio, Francesco L. and Parrinello, Michele }, citeulike-article-id = {2946065}, doi = {http://dx.doi.org/10.1021/ja801792g}, journal = {J. Am. Chem. Soc.}, keywords = {kirbac, lipids, md, selectivity, simulation}, month = {June}, posted-at = {2008-07-01 00:10:09}, priority = {2}, title = {Conformational Changes and Gating at the Selectivity Filter of Potassium Channels}, url = {http://dx.doi.org/10.1021/ja801792g}, year = {2008} }

TY - JOUR ID - citeulike:2946065 L3 - citeulike-article-id:2946065 N2 - Abstract: The translocation of ions and water across cell membranes is a prerequisite for many of lifes processes. K+ channels are a diverse family of integral membrane proteins through which K+ can pass selectively. There is an ongoing debate about the nature of conformational changes associated with the opening and closing and conductive and nonconductive states of potassium (K+) channels. These changes depend on the membrane potential, the K+ concentration gradient, and large scale motions of transmembrane helices and associated residues. Experiments also suggest that local structural changes in the selectivity filter may act as the dominant gate referred to as C-type inactivation. Herein we present an extensive computational study on KirBac, which supports the existence of a physical gate or constriction in the selectivity filter (SF) of K+ channels. Our computations identify a new selectivity filter structure, which is likely associated with C-type inactivation. Specifically, the four peptide chains that comprise the filter adopt an unusual structure in which their dihedrals alternate between left- and right-handed Ramachandran angles, which also justifies the need for conservation of glycine in the K+ selectivity filter, since it is the only residue able to play this bifunctional role. JF - J. Am. Chem. Soc. AD - Physical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, U.K., Center for Molecular Modelling and Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pensylvannia 19104-6323, and Department of Chemistry and Applied Biosciences, ETH Zurich, USI - Campus, via Giuseppe Buffi 13, 6900 Lugano, Switzerland TI - Conformational Changes and Gating at the Selectivity Filter of Potassium Channels KW - kirbac KW - lipids KW - md KW - selectivity KW - simulation AU - Domene, Carmen AU - Klein, Michael AU - Branduardi, Davide AU - Gervasio, Francesco AU - Parrinello, Michele PY - 2008/06/28/ UR - http://dx.doi.org/10.1021/ja801792g ER -