Structure of Potassium Channels 3D Models by Professor Roderick MacKinnon, Rockefeller University

The gene for potassium channels from the bacterium Streptomyces was cloned and expressed as a protein. The protein was crystallized (the hard part!), analyzed by x-ray crystallography, and its structure was reconstructed in three dimensions. In 2005, the same laboratory (headed by Rod MacKinnon, who received the Nobel Prize in 2003) published a structure for the Shaker K channel, a much more complex voltage-dependent channel found in higher animals.

A complete K channel is a tetramer of 4 identical proteins that together form a pore for potassium ions. For the bacterial channel, each protein has two helices that span the membrane, plus a loop that lines the pore. The voltage dependent Shaker channel has six transmembrane helices, a loop that lines the pore, and two large additional regions (the T1 and Beta domains) that project into the cytoplasm.

The channel is selective for potassium ions because of a narrow "selectivity filter" at the extracellular end (top) of the pore. The filter is just the right size to surround potassium ions with a ring of carbonyl oxygens, which take the place of the water molecules that are normally bound to an ion. This allows a "naked" ion to slip through the filter. Smaller ions like Na+ are too small to fit tightly in the "oxygen cage," so they do not lose their surrounding water molecules and cannot pass through the filter.

For a concise minireview, see: MacKinnon, R (2003) Potassium channels. Febs Letters 555: 62-65.

Videos

Requires free QuickTime Plug-In or Flash Plug-In (last video only). Each video will open in a new tab or window. If your screen is large enough to show the entire frame and the player's controls, you can pause the playback and slide the control to rotate the protein yourself.

Web-friendly composite. (QuickTime, 16.8 MB) This version combines all four of the other videos (below) in a smaller format that begins playing quickly, repeats each sequence, and has explanatory titles. (Note that the last sequence, the close-up of K ions in the selectivity filter, is distorted by being stretched horizontally. This is an artifact of requiring this section to have the same frame size as the other three sections.)

Basic structure of the channel. (QuickTime, 17.7 MB) Each of the four proteins in the tetramer is given a different color for clarity. You can see that each protein subunit has two helical transmembrane segments and a loop that helps form the selectivity filter.

Path of K ions through a channel. (QuickTime, 3.7 MB) The ions are shown as green balls. For each protein subunit, the inner helix is red, the outer helix is blue, and the pore loop is yellow.

Another view of K ions in the channel. (QuickTime, 3.9 MB) In this model, the protein's structure is shown in yellow, with the K+ ions as blue spheres. Note the large aequeous cavity at the midpoint of the channel, where an ion can be surrounded by water.

Close-up of K ions in the selectivity filter. (Flash, 100 KB) Two potassium ions (green) occupy the filter simultaneously, each surrounded by eight carbonyl oxygens (red). The ions repel each other, so that when a new one pops into the filter, another ion pops out at the other end. Ions can pass either way through the filter.

Diagrams

Shaker K channel structure (Long, Campbell & MacKinnon, 2005)

Kv1.2 channel, top view, showing S4 helix in blue and S6 in red (Nature, 2007)

Closed and open positions of the pore (MacKinnon, 2003)

3 models for S4 movements: helical screw, transporter, and paddle (Borjesson & Elinder, 2008)

Handout showing still figures of K-channel structures (PDF format, 2.7 MB).