Control of ion selectivity in potassium channels by electrostatic and dynamic properties of carbonyl ligands

  title={Control of ion selectivity in potassium channels by electrostatic and dynamic properties of carbonyl ligands},
  author={Sergei Yu. Noskov and Simon Bern{\`e}che and Beno{\^i}t Roux},
Potassium channels are essential for maintaining a normal ionic balance across cell membranes. Central to this function is the ability of such channels to support transmembrane ion conduction at nearly diffusion-limited rates while discriminating for K+ over Na+ by more than a thousand-fold. This selectivity arises because the transfer of the K+ ion into the channel pore is energetically favoured, a feature commonly attributed to a structurally precise fit between the K+ ion and carbonyl groups… 

The predominant role of coordination number in potassium channel selectivity.

It is demonstrated that the number of carbonyl oxygen atoms that surround permeating ions is the most important factor in determining ion selectivity rather than the size of the pore or the strength of the coordinating dipoles.

Tuning a potassium channel--the caress of the surroundings.

In this issue, Varma and Rempe provide a novel explanation for K+ and Na+ binding to clusters of water and of a few other ligands, and find that preferred solvation structures are sensitive to their environment, providing new insight into factors controlling selectivity.

Selectivity in K+ channels is due to topological control of the permeant ion's coordinated state

A simple theoretical analysis of K+ and Na+ complexation with water in the context of simplified binding site models and bulk solution reveals that water molecules and carbonyl groups can both provide K+ selective environments if equivalent constraints are imposed on the coordination number of the complex.

Mechanism of ion permeation and selectivity in a voltage gated sodium channel.

Na(+) conduction is shown to involve the loosely coupled "knock-on" movement of two solvated ions, and mechanisms are different to those described for K(+) channels, highlighting the importance of developing a separate mechanistic understanding of Na(+) and Ca(2+) channels.

Mechanism of potassium-channel selectivity revealed by Na+ and Li+ binding sites within the KcsA pore

It is proposed that selective permeation from the intracellular side primarily results from a large energy barrier blocking filter entry for Na+ and Li+ in the presence of K+, not from a difference of binding affinity between ions.

Ion channels and ion selectivity Essays in Biochemistry

A deeper analysis shows that subtle effects play an important role in these flexible dynamical structures, including the ability to remain highly selective for K+ over Na+ while allowing high-throughput ion conduction at a rate close to the diffusion limit.

Incidence of partial charges on ion selectivity in potassium channels.

How differences in polarization effects in the adducts with K(+) and Na(+) can play a role as for ionic selectivity and conductance is discussed.

Non-Equilibrium Dynamics Contribute to Ion Selectivity in the KcsA Channel

A mechanistic model of ion selectivity by this channel relates the structural rearrangement of the selectivity filter to the differential dehydration of ions and multiple-ion occupancy and describes a mechanism to efficiently select and conduct K+.

Engineering differential charge selectivity from a single structural template

A detailed analysis of the literature reveals that a large number of discrepancies exist and that no consensus mechanism has yet been attained as to whether charge selectivity is governed by interactions of the permeating ions with backbone atoms or side-chain atoms.



The structure of the potassium channel: molecular basis of K+ conduction and selectivity.

The architecture of the pore establishes the physical principles underlying selective K+ conduction, which promotes ion conduction by exploiting electrostatic repulsive forces to overcome attractive forces between K+ ions and the selectivity filter.

Probing ion permeation and gating in a K+ channel with backbone mutations in the selectivity filter

It is demonstrated that K+ ion selectivity can be retained even with significant reduction of electronegativity in the selectivity filter, and that conformational changes of the filter arising from interactions between permeant ions and the backbone carbonyls contribute directly to channel gating.

Chemistry of ion coordination and hydration revealed by a K+ channel–Fab complex at 2.0 Å resolution

Here it is shown how the K+ channel displaces water molecules around an ion at its extracellular entryway, and how it holds a K+ ion in a square antiprism of water molecules in a cavity near its intracellular entry way.

Potassium and sodium binding to the outer mouth of the K+ channel.

Molecular dynamics simulations of the K+ channel from Streptomyces lividans were performed in a membrane-mimetic environment with Na+ and K+ in different initial locations and the hydration state of the metal ions turned out to depend significantly on the conformational flexibility of the channel.

Energetics of ion conduction through the K+ channel

It is found that ion conduction involves transitions between two main states, with two and three K+ ions occupying the selectivity filter, respectively; this process is reminiscent of the ‘knock-on’ mechanism proposed by Hodgkin and Keynes in 1955.

Ion permeation mechanism of the potassium channel

Results from molecular dynamics free energy perturbation calculations that both establish the nature of the multiple ion conduction mechanism and yield the correct ion selectivity of the K+ channel are reported.

Conduction and selectivity in potassium channels

Ion channels are integral membrane proteins spanning the lipid bilayer and necessarily communicating with both aqueous phases, and may be considered as enzymes, in that they reduce the energies of transmembrane ionic diffusion from the 250 kJ/mol above to values in the range of 20 kj/mol a rate enhancement of about 1039.

The potassium channel: Structure, selectivity and diffusion

Evidence that acidic and basic sidechains may dissociate in the presence of multiple K+ ions to explain experimental ion density maps is found, supporting the high channel currents observed experimentally.