APS March Meeting 2014
Volume 59, Number 1
Monday–Friday, March 3–7, 2014;
Denver, Colorado
Session W32: Invited Session: Quantum Mechanics Applied to Biophysical Problems
2:30 PM–5:30 PM,
Thursday, March 6, 2014
Room: 708-712
Sponsoring
Units:
DCOMP DBIO
Chair: Susan Rempe, Sandia National Laboratories
Abstract ID: BAPS.2014.MAR.W32.1
Abstract: W32.00001 : Principles Governing Metal Ion Selectivity in Ion Channel Proteins
2:30 PM–3:06 PM
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Abstract
Author:
Carmay Lim
(Institute of Biomedical Sciences, Academia Sinica)
Our research interests are to
\begin{enumerate}
\item (i) unravel the principles governing biological processes and use them to identify novel drug targets and guide drug design, and
\item (ii) develop new methods for studying macromolecular interactions.
\end{enumerate}
This talk will provide an overview of our work in these two areas and an
example of how our studies have helped to unravel the principles underlying
the conversion of Ca$^{2+}$-selective to
Na$^{+}$-selective channels. Ion selectivity of four-domain
voltage-gated Ca$^{2+}$(Ca$_{\mathrm{v}})$ and sodium
(Na$_{\mathrm{v}})$ channels, which is controlled by the selectivity filter
(SF, the narrowest region of an open pore), is crucial for electrical
signaling. Over billions of years of evolution, mutation of the Glu from
domain II/III in the \textbf{EEEE}/\textbf{DEEA} SF of
Ca$^{2+}$-selective Ca$_{\mathrm{v}}$ channels to Lys made these
channels Na$^{+}$-selective. This talk will delineate the physical
principles why Lys is sufficient for
Na$^{+}$/Ca$^{2+}$selectivity and why the \textbf{DEKA} SF
is more Na$^{+}$-selective than the \textbf{DKEA} one.
\\[4pt]
References:\\[0pt]
[1] Competition among metal ions for protein binding sites: Determinants of metal ion selectivity in proteins. Todor Dudev {\&} Carmay Lim, \textit{Chemical Reviews} (\textbf{2013}) http://dx.doi.org/10.1021/cr4004665\\[0pt]
[2] Effect of Metal Hydration on the Selectivity of Mg$^{2+}$ vs. Ca$^{2+}$ in Magnesium Ion Channels. Todor Dudev {\&} Carmay Lim \textit{J. Am. Chem. Soc.}\textbf{ (2013) }\underline {135}: 17200-17208. \\[0pt]
[3] Competition among Ca$^{\mathrm{2+}}$, Mg$^{2+}$, and Na$^{+}$ for ion channel selectivity filters: Determinants of metal ion selectivity. Todor Dudev {\&} Carmay Lim,$ J$. \textit{Phys. Chem. B} (\textbf{2012)} \underline {116}: 10703--10714.\\[0pt]
[4] Why voltage-gated Ca$^{2+}$ and bacterial Na$^{+}$ channels with the same EEEE motif in their selectivity filters confer opposite metal selectivity. Todor Dudev {\&} Carmay Lim,\textit{ Phys. Chem. Chem. Phys. }(\textbf{2012)}\underline { 14}: 12451--12456.
To cite this abstract, use the following reference: http://meetings.aps.org/link/BAPS.2014.MAR.W32.1