Diffusion of Potassium Ions through the KcsA K+ Channel
Ion channels assist and control the diffusion of ions through biological membranes. Potassium channels permit millions of potassium ions -- but not sodium ions -- to cross the membrane per second. How is such remarkable selectivity achieved given that the ionic radius of Na+ is 0.4 Å smaller than that of K+?
The protein stabilizes dehydrated potassium ions in the selectivity filter. The structure of the KcsA K+ channel reveals eight oxygens surrounding each ion binding site, with four oxygens above and four below each site. These eight oxygen ligands are organized as twisted cube and thus are a beautiful mimic of the inner hydration shell of the potassium ion.
Twenty oxygen atoms (red) line the wall of the selectivity filter. The backbone of each polypeptide chains is colored green. One fully hydrated K+ (purple) is poised at the entrance to the selectivity filter. It is loosely held in a distinct negative potential energy well created by the protein microenvironment. All the waters in the second hydration shell are disordered and are not visible.
Note that all the oxygen atoms of the protein are from the axis, just as the water molecules in the first hydration shell. Thus, the oxygen atoms of the protein are positioned to stabilize dehydrated potassium ions as they diffuse through the selectivity filter.
Hydration of "free" potassium ion vs. "solvation" of ion in the selectivity filter. "twisted cube" traces.
A hydrated sodium ion is too large to fit through the selectivity filter, and a desolvated sodium ion, because of its smaller ionic radius, would only interact with two or three oxygen atoms if it were in the selectivity filter. Thus, Na+ is more stable in an aqueous environment than it would be in the selectivity filter.
There are four binding sites for K+ in the selectivity filter. The ions are stripped of their hydration shells as they enter the selectivity and then resolvated by oxygen atoms in the filter. At each site the K+ is coordinated to 8 oxygen atoms. The cation jumps from one site to another.
flux of potassium ions.
The selectivity filter is flexible enough so that the carbonyls that substitute for the hydration shell can move slightly as a K+ ion jumps from one site to the next. However, the filter cannot adopt a conformation which would allow dehydration of sodium ions.
The protein provides substantial stabilization to the potassium ions through ion-dipole interactions with protein backbone carbonyl groups, thereby compensating them for their loss of very favorable interactions with water outside the membrane.
Ions in aqueous solutions are hydrated through strong ion-dipole interactions with the water dipole. The first hydration shell is very labile, is in fast exchange with the second shell, and is not rigid. The hydration of ions has a strong influence on charge-charge and charge-dipole interactions and plays a dominant role in such matters as binding of cations to negatively charged groups in proteins and nucleic acids.
The hydration shell around charged groups in proteins and nucleic acids always involves hydrogen bonding as well as charge-charge interactions.
Ionic hydration dynamics play a central role in the mechanism of ion transport through membrane ion channels. The selectivity filter of K+ channel provides substantial stabilization to the potassium ions through ion-dipole interactions with protein backbone carbonyl groups, thereby compensating them for their loss of very favorable interactions with water outside the membrane. A solvated sodium ion is too large to fit through the selectivity filter, and a desolvated sodium ion, because of its smaller ionic radius, would only interact with two or three oxygen atoms if it were in the selectivity filter. Thus, a fully hydrated Na+ is more stable outside the K+ channel than it would be in the selectivity filter.