K⁺ Selectivity Pore

Close-up: Only three of the subunits are shown to provide a clearer view of the pore. All seven of the possible K⁺ locations are shown. However, only four, at most, are occupied at the same time; the other sites contain waters. Residues 75-79 comprise the selectivity pore and are shown as Sticks, colored CPK. The mainchain C=O's of these residues coordinate the K⁺ ions. The water-filled cavity is colored cyan. All of the waters shown here are highly-ordered and thus differ from the "bulk" water surrounding the channel.

K⁺ at sites 2 & 4: Each K⁺ ion is coordinated by eight oxygens with water between them. For example, K⁺ at site 4 is coordinated by the side chains and C=O's of Thr 75.

K⁺ between sites: The K⁺ ions are coordinated by only four of the mainchain C=O's. For example, the K⁺ between sites 2 and 3 is coordinated only by Val 76. A K⁺ is about to enter the pore from the cavity.

K⁺ at sites 1 & 3: The K⁺ ions are coordinated by eight mainchain C=O's. For example, K⁺ at site 1 is coordinated by Gly 77 and Tyr 78.
The pore is normally occupied by two K⁺ ions and two waters. Concerted movement of the two ions and their waters leads to K⁺ exit from, or entry into the cell. The scripted animation shows the sequence of steps in the exit pathway.

K⁺ Efflux Mechanism
The steps shown in the animation (See Morais-Cabral et al., Figs. 4 and 5.):

State I   Water-filled pore: The K⁺ that will soon exit is in the cavity.

State H   K⁺ at site 4: The K⁺ enters the pore and is replaced by another in the cavity.

State E   K⁺ at site 3: The K⁺ moves up one position (with the waters). Another K⁺ occupies the cavity from the cytosol.

State C   K⁺ at sites 2 & 4: The K⁺ moves up another position.

Intermediate between site 2 and the extracellular site: The K⁺ is coordinated by only four of the mainchain C=O's prior to dissociation, first by Tyr 78 and finally by Gly 79.

Dissociation from extracellular site: The K⁺ binds briefly at site 0 and at the fully hydrated extracellular site, then diffuses into the extracellular solution.

Script ends with K⁺ at sites 2 & 4. For multiple cycles of ion efflux, the pathway resumes at State C above. K⁺ entry follows the same pathway in reverse direction. A single cycle takes about 10 nanoseconds to complete!

The refined structure of the potassium channel is described by:
Zhou, Y. Morais-Cabral, J. H. Kaufman, A. & MacKinnon, R. (2001) "Chemistry of ion coordination and hydration revealed by a K⁺ channel-Fab complex at 2.0 Å resolution". Nature 414: 43     PubMed [1K4C.pdb]
(A "fake" coordinate file containing the K⁺ ions and water used for the animation was added to 1K4C.pdb as Model 2.)
The ion-conduction pathways are described by:
Morais-Cabral, J. H. Zhou, Y. & MacKinnon, R. (2001) "Energetic optimization of ion conduction rate by the K⁺ selectivity filter" Nature 414: 37     PubMed
References to Figs. above are to those of Morais-Cabral et al.)