Abstract
Calcium channels have highly charged selectivity filters (4 COO- groups) that attract cations in to balance this charge and minimize free energy, forcing the cations (Na+ and Ca2+) to compete for space in the filter. A reduced model was developed to better understand the mechanism of ion selectivity in calcium channels. The charge/space competition (CSC) mechanism implies that Ca2+ is more efficient in balancing the charge of the filter because it provides twice the charge as Na+ while occupying the same space. The CSC mechanism further implies that the main determinant of Ca2+ versus Na+ selectivity is the density of charged particles in the selectivity filter, i.e., the volume of the filter (after fixing the number of charged groups in the filter). In this paper we test this hypothesis by changing filter length and/or radius (shape) of the cylindrical selectivity filter of our reduced model. We show that varying volume and shape together has substantially stronger effects than varying shape alone with volume fixed. Our simulations show the importance of depletion zones of ions in determining channel conductance calculated with the integrated Nernst-Planck equation. We show that confining the protein side chains with soft or hard walls does not influence selectivity.
| Original language | English |
|---|---|
| Pages (from-to) | 2471-2480 |
| Number of pages | 10 |
| Journal | Biochimica et Biophysica Acta - Biomembranes |
| Volume | 1788 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 1 2009 |
| Externally published | Yes |
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Keywords
- Calcium channel
- Grand canonical
- Monte Carlo simulation
- Permeation
- Selectivity
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Biophysics
Cite this
Protein structure and ionic selectivity in calcium channels : Selectivity filter size, not shape, matters. / Malasics, Attila; Gillespie, Dirk; Nonner, Wolfgang; Henderson, Douglas; Eisenberg, Bob; Boda, Dezso.
In: Biochimica et Biophysica Acta - Biomembranes, Vol. 1788, No. 12, 01.12.2009, p. 2471-2480.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Protein structure and ionic selectivity in calcium channels
T2 - Selectivity filter size, not shape, matters
AU - Malasics, Attila
AU - Gillespie, Dirk
AU - Nonner, Wolfgang
AU - Henderson, Douglas
AU - Eisenberg, Bob
AU - Boda, Dezso
PY - 2009/12/1
Y1 - 2009/12/1
N2 - Calcium channels have highly charged selectivity filters (4 COO- groups) that attract cations in to balance this charge and minimize free energy, forcing the cations (Na+ and Ca2+) to compete for space in the filter. A reduced model was developed to better understand the mechanism of ion selectivity in calcium channels. The charge/space competition (CSC) mechanism implies that Ca2+ is more efficient in balancing the charge of the filter because it provides twice the charge as Na+ while occupying the same space. The CSC mechanism further implies that the main determinant of Ca2+ versus Na+ selectivity is the density of charged particles in the selectivity filter, i.e., the volume of the filter (after fixing the number of charged groups in the filter). In this paper we test this hypothesis by changing filter length and/or radius (shape) of the cylindrical selectivity filter of our reduced model. We show that varying volume and shape together has substantially stronger effects than varying shape alone with volume fixed. Our simulations show the importance of depletion zones of ions in determining channel conductance calculated with the integrated Nernst-Planck equation. We show that confining the protein side chains with soft or hard walls does not influence selectivity.
AB - Calcium channels have highly charged selectivity filters (4 COO- groups) that attract cations in to balance this charge and minimize free energy, forcing the cations (Na+ and Ca2+) to compete for space in the filter. A reduced model was developed to better understand the mechanism of ion selectivity in calcium channels. The charge/space competition (CSC) mechanism implies that Ca2+ is more efficient in balancing the charge of the filter because it provides twice the charge as Na+ while occupying the same space. The CSC mechanism further implies that the main determinant of Ca2+ versus Na+ selectivity is the density of charged particles in the selectivity filter, i.e., the volume of the filter (after fixing the number of charged groups in the filter). In this paper we test this hypothesis by changing filter length and/or radius (shape) of the cylindrical selectivity filter of our reduced model. We show that varying volume and shape together has substantially stronger effects than varying shape alone with volume fixed. Our simulations show the importance of depletion zones of ions in determining channel conductance calculated with the integrated Nernst-Planck equation. We show that confining the protein side chains with soft or hard walls does not influence selectivity.
KW - Calcium channel
KW - Grand canonical
KW - Monte Carlo simulation
KW - Permeation
KW - Selectivity
UR - http://www.scopus.com/inward/record.url?scp=71849109100&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=71849109100&partnerID=8YFLogxK
U2 - 10.1016/j.bbamem.2009.09.022
DO - 10.1016/j.bbamem.2009.09.022
M3 - Article
C2 - 19818330
AN - SCOPUS:71849109100
VL - 1788
SP - 2471
EP - 2480
JO - Biochimica et Biophysica Acta - Biomembranes
JF - Biochimica et Biophysica Acta - Biomembranes
SN - 0005-2736
IS - 12
ER -