[en] The chemical property of methyl groups that renders them indispensable to biomolecules is their hydrophobicity. Quantum mechanical studies undertaken here to understand the effect of point substitutions on potassium (K-) channels illustrate quantitatively how methyl-induced polarization also contributes to biomolecular function. K- channels regulate transmembrane salt concentration gradients by transporting K+ ions selectively. One of the K+ binding sites in the channel's selectivity filter, the S4 site, also binds Ba2+ ions, which blocks K+ transport. This inhibitory property of Ba2+ ions has been vital in understanding K-channel mechanism. In most K-channels, the S4 site is composed of four threonine amino acids. The K channels that carry serine instead of threonine are significantly less susceptible to Ba2+ block and have reduced stabilities. We find that these differences can be explained by the lower polarizability of serine compared with threonine because serine carries one less branched methyl group than threonine. A T -> S substitution in the S4 site reduces its polarizability, which, in turn, reduces ion binding by several kilocalories per mole. Although the loss in binding affinity is high for Ba2+, the loss in K+ binding affinity is also significant thermodynamically, which reduces channel stability. These results highlight, in general, how biomolecular function can rely on the polarization induced by methyl groups especially those that are proximal to charged moieties, including ions titratable amino acids, sulfates, phosphates, and nucleotides.
Disciplines :
Physical, chemical, mathematical & earth Sciences: Multidisciplinary, general & others
Author, co-author :
Rossi, Mariana; Theory Department, Fritz Haber Institute of the Max Planck Society, 14195 Berlin, Germany
Tkatchenko, Alexandre ; Theory Department, Fritz Haber Institute of the Max Planck Society, 14195 Berlin, Germany
Rempe, Susan B.; Biological and Materials Sciences Center, Sandia National Laboratories, Albuquerque, NM 87185
Sameer, Varma; Biological and Materials Sciences Center, Sandia National Laboratories, Albuquerque, NM 87185 ; Department of Cell Biology, Microbiology, and Molecular Biology, and Department of Physics, University of South Florida, Tampa, FL 33620
External co-authors :
yes
Language :
English
Title :
Role of methyl-induced polarization in ion binding
Publication date :
2013
Journal title :
Proceedings of the National Academy of Sciences of the United States of America
ISSN :
0027-8424
Publisher :
NATL ACAD SCIENCES, 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA, Unknown/unspecified