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An entropic mechanism of generating selective ion binding in macromolecules.

Thomas M, Jayatilaka D, Corry B - PLoS Comput. Biol. (2013)

Bottom Line: Several mechanisms have been proposed to explain how ion channels and transporters distinguish between similar ions, a process crucial for maintaining proper cell function.Each operates in subtly different ways yet can produce markedly different influences on ion selectivity.Simple abstract-ligand models, as well as simple models based upon the ion binding sites in two amino acid transporters, show that limiting ligand fluctuations can create ion selectivity between Li(+), Na(+) and K(+) even when there is no strain associated with the molecular framework accommodating the different ions.

View Article: PubMed Central - PubMed

Affiliation: Research School of Biology, Australian National University, Canberra, Australia.

ABSTRACT
Several mechanisms have been proposed to explain how ion channels and transporters distinguish between similar ions, a process crucial for maintaining proper cell function. Of these, three can be broadly classed as mechanisms involving specific positional constraints on the ion coordinating ligands which arise through: a "rigid cavity", a 'strained cavity' and 'reduced ligand fluctuations'. Each operates in subtly different ways yet can produce markedly different influences on ion selectivity. Here we expand upon preliminary investigations into the reduced ligand fluctuation mechanism of ion selectivity by simulating how a series of model systems respond to a decrease in ligand thermal fluctuations while simultaneously maintaining optimal ion-ligand binding distances. Simple abstract-ligand models, as well as simple models based upon the ion binding sites in two amino acid transporters, show that limiting ligand fluctuations can create ion selectivity between Li(+), Na(+) and K(+) even when there is no strain associated with the molecular framework accommodating the different ions. Reducing the fluctuations in the position of the coordinating ligands contributes to selectivity toward the smaller of two ions as a consequence of entropic differences.

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A decomposition of(magenta), in the absence of cavity strain, into(black) and(brown) components of ion selectivity between Na+ and K+ for (A) 5 fold, (B) 6 fold, (C) 7 fold and (D) 8 fold coordination states. The red region indicates a contribution toward K+ selectivity, while the blue region indicates a contribution toward Na+ selectivity.
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pcbi-1002914-g003: A decomposition of(magenta), in the absence of cavity strain, into(black) and(brown) components of ion selectivity between Na+ and K+ for (A) 5 fold, (B) 6 fold, (C) 7 fold and (D) 8 fold coordination states. The red region indicates a contribution toward K+ selectivity, while the blue region indicates a contribution toward Na+ selectivity.

Mentions: A more subtle situation arises when the position of the restraint is different for each ion, i.e. when we consider the RLF mechanism without any strain. Although the difference looks small on the scale of Fig. 1, a 2–5 kcal/mol increase in selectivity toward Na+ occurs for the exchange reaction with K+ with ligands when the size of the thermal fluctuations is reduced ( increased). The majority of this change occurs for between and , plateauing for (see Fig. 3 to see this plotted in a different scale). This change in ion selectivity alters these models from K+ selective sites to Na+ or non-selective sites. For , the selectivity in the already K+ selective site is further enhanced by 2–3 kcal/mol.


An entropic mechanism of generating selective ion binding in macromolecules.

Thomas M, Jayatilaka D, Corry B - PLoS Comput. Biol. (2013)

A decomposition of(magenta), in the absence of cavity strain, into(black) and(brown) components of ion selectivity between Na+ and K+ for (A) 5 fold, (B) 6 fold, (C) 7 fold and (D) 8 fold coordination states. The red region indicates a contribution toward K+ selectivity, while the blue region indicates a contribution toward Na+ selectivity.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3585399&req=5

pcbi-1002914-g003: A decomposition of(magenta), in the absence of cavity strain, into(black) and(brown) components of ion selectivity between Na+ and K+ for (A) 5 fold, (B) 6 fold, (C) 7 fold and (D) 8 fold coordination states. The red region indicates a contribution toward K+ selectivity, while the blue region indicates a contribution toward Na+ selectivity.
Mentions: A more subtle situation arises when the position of the restraint is different for each ion, i.e. when we consider the RLF mechanism without any strain. Although the difference looks small on the scale of Fig. 1, a 2–5 kcal/mol increase in selectivity toward Na+ occurs for the exchange reaction with K+ with ligands when the size of the thermal fluctuations is reduced ( increased). The majority of this change occurs for between and , plateauing for (see Fig. 3 to see this plotted in a different scale). This change in ion selectivity alters these models from K+ selective sites to Na+ or non-selective sites. For , the selectivity in the already K+ selective site is further enhanced by 2–3 kcal/mol.

Bottom Line: Several mechanisms have been proposed to explain how ion channels and transporters distinguish between similar ions, a process crucial for maintaining proper cell function.Each operates in subtly different ways yet can produce markedly different influences on ion selectivity.Simple abstract-ligand models, as well as simple models based upon the ion binding sites in two amino acid transporters, show that limiting ligand fluctuations can create ion selectivity between Li(+), Na(+) and K(+) even when there is no strain associated with the molecular framework accommodating the different ions.

View Article: PubMed Central - PubMed

Affiliation: Research School of Biology, Australian National University, Canberra, Australia.

ABSTRACT
Several mechanisms have been proposed to explain how ion channels and transporters distinguish between similar ions, a process crucial for maintaining proper cell function. Of these, three can be broadly classed as mechanisms involving specific positional constraints on the ion coordinating ligands which arise through: a "rigid cavity", a 'strained cavity' and 'reduced ligand fluctuations'. Each operates in subtly different ways yet can produce markedly different influences on ion selectivity. Here we expand upon preliminary investigations into the reduced ligand fluctuation mechanism of ion selectivity by simulating how a series of model systems respond to a decrease in ligand thermal fluctuations while simultaneously maintaining optimal ion-ligand binding distances. Simple abstract-ligand models, as well as simple models based upon the ion binding sites in two amino acid transporters, show that limiting ligand fluctuations can create ion selectivity between Li(+), Na(+) and K(+) even when there is no strain associated with the molecular framework accommodating the different ions. Reducing the fluctuations in the position of the coordinating ligands contributes to selectivity toward the smaller of two ions as a consequence of entropic differences.

Show MeSH
Related in: MedlinePlus