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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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The effect of reducing the size of the ligand thermal fluctuations on selectivity between Li+ and Na (solid magenta line) with increasing harmonic constraint constant,for (A) 4 fold, (B) 5 fold, (C) 6 fold and (D) 7 fold coordination states. These are compared with a strained cavity model at ion-ligand distance optimised for Li+ (dotted green line) and Na+ (dotted blue line). A negative value (blue region) of  indicates the model site is selective for Na+, a positive value (green region) indicates Li+ selectivity.
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pcbi-1002914-g002: The effect of reducing the size of the ligand thermal fluctuations on selectivity between Li+ and Na (solid magenta line) with increasing harmonic constraint constant,for (A) 4 fold, (B) 5 fold, (C) 6 fold and (D) 7 fold coordination states. These are compared with a strained cavity model at ion-ligand distance optimised for Li+ (dotted green line) and Na+ (dotted blue line). A negative value (blue region) of indicates the model site is selective for Na+, a positive value (green region) indicates Li+ selectivity.

Mentions: The ion selectivity of the abstract models, including contributions from the RLF mechanism, is plotted versus the force constant, , for binding sites with 4–8 ligands in Fig. 1 and 2. For comparison we also plot two sets of results for the strained cavity mechanism, that is, when the same location of the restraint is used for both ions rather than using an ‘optimal’ position for each ion type.


An entropic mechanism of generating selective ion binding in macromolecules.

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

The effect of reducing the size of the ligand thermal fluctuations on selectivity between Li+ and Na (solid magenta line) with increasing harmonic constraint constant,for (A) 4 fold, (B) 5 fold, (C) 6 fold and (D) 7 fold coordination states. These are compared with a strained cavity model at ion-ligand distance optimised for Li+ (dotted green line) and Na+ (dotted blue line). A negative value (blue region) of  indicates the model site is selective for Na+, a positive value (green region) indicates Li+ selectivity.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1002914-g002: The effect of reducing the size of the ligand thermal fluctuations on selectivity between Li+ and Na (solid magenta line) with increasing harmonic constraint constant,for (A) 4 fold, (B) 5 fold, (C) 6 fold and (D) 7 fold coordination states. These are compared with a strained cavity model at ion-ligand distance optimised for Li+ (dotted green line) and Na+ (dotted blue line). A negative value (blue region) of indicates the model site is selective for Na+, a positive value (green region) indicates Li+ selectivity.
Mentions: The ion selectivity of the abstract models, including contributions from the RLF mechanism, is plotted versus the force constant, , for binding sites with 4–8 ligands in Fig. 1 and 2. For comparison we also plot two sets of results for the strained cavity mechanism, that is, when the same location of the restraint is used for both ions rather than using an ‘optimal’ position for each ion type.

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