K-Channels...  Many cell membranes hold embedded channel proteins.  K+ channels help
        control the electrical potential across cell membranes by catalyzing the rapid, selective
        (K+ only) diffusion of K+ ions down their electrochemical gradient.
            Ion channel proteins must remove an ion's hydration shell to provide ion selectivity
            & rapid throughput, i.e., single file passage of charged ions at high rates.

        Using X-ray crystallographic ion distribution of K+ & Rb+ and ion conduction measurements
        Rod MacKinnon's group at Rockefeller Univ., in Nov 2001, took the first atomic-resolution
        pictures of a K+ channel  at a resolution of 2 angstrom.
            K+ channel has 2 main parts:    1) a cavity site holding a hydrated K+ ion &  
            2) an oxygen-lined electronegative tunnel in which dehydrated K+ fits precisely. 
            The channels interior mimics the hydration sphere of water around an ion in solution,
            & catalyzes the dehydration, transfer, & rehydration of K+ ion in 10 nanoseconds.   
        The current molecular representation of the K+ ion channel...   K+ channel Model

        The free-energy barrier is near2-3 Kcal/mol, thus ion conduction is limited only by diffusion.   
                        Proposed  mechanism of action  has 1 K+ ion entering the selectivity filter
back                     displacing the K+ ion on the opposite side 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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(a) There are seven main sites for ions along the pore axis: one in the hydrated cavity site [see figure]  (12 angstrom radius), four in the selectivity filter and two just beyond the external end of the pore (8 angstrom radius).

The cavity site is fully occupied and mimics the embrace of water molecules in normal hydration sphere of ion in solution; but (as indicated in b) dehydration occurs as ion enters filter [see figure], where only half of the remaining six are occupied at any one time.

(b) There are two main ion configurations, known as outer and inner, that are postulated to exist within the slectivity pore. Purple arrows indicate ion shifts that are linked directly to concerted ion entry into and exit from the pore. Red arrows represent shifts within the pore without ion entry and exit. As shown here, then, ion passage through the selectivity filter and extracellular sites occurs in bucket-brigade fashion.   [fig]

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Molecular representation of the atomic model of the K+ channel embedded in an reconstituted DPPC phosphilipid bilayer membrane bathed by a 150 mM KCl aqueous salt solution.

 

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A ribbon representation of the K channel. Potassium ions (green spheres) bind at four locations in the selectivity filter (yellow) and in the water-filled cavity site at the membrane center (bottom ion).

A close-up view of the selectivity filter in ball-and-stick representation. The four K+ ions are numbered to indicate the location of binding sites in the filter; position 1 is closest to the extracellular solution and position 4 is closest to the cavity. Key amino acids forming the selectivity filter are shown.

      Morais-Cabral, Zhou, & MacKinnon in
       Nature  414:37-42, 2001

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  Stereo view of a hydrated K+ ion in the central cavity site. Eight water molecules (red spheres) surround a single K+ ion (green sphere) in the cavity. Residues forming the cavity are shown in ball-and-stick representation. For clarity, only backbone atoms and the side chains facing the cavity (Thr 75, Ile 100, Phe 103, Gly 104 and Thr 107).

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Dehydration. Stereo view of entryway to selectivity filter.  4 carboxyls provide 4 negative charges near entryway, making it quite electronegative & attractive to a cation. The selectivity filter exists in 2 configurations. When  configuration of ions (green spheres) & water (red spheres) inside the filter is K+-water-K+-water (left; 1,3 configuration - fully hydrated), an ion at the entryway is displaced further away. When configuration is water-K+-water-K+ (right; 2,4 configuration), the ion outside the filter is drawn closer to the pore, the carbonly oxygen atom (G79) help displace half of the K-ion's hydration shell.

 

 

 

 

 

 

 

 

 

 

 

 

 

Miller, C.  See Potassium Run.  Nature 414, 23-24 (2001)

Morais-Cabral, J. H.,  Zhou, Y.,  and MacKinnon, R.  Energetic optimization of ion
        conduction rate by the K+ selectivity filter.   Nature 414, 37-42 (2001).  

Zhou, Y.,  Morais-Cabral, J. H.,  Kaufman, A., and MacKinnon, R.
        Chemistry of ion coordination and hydration revealed by a K+ channel-Fab
        complex at 2.0 Å  resolution.   Nature 414, 43-48 (2001).

Berneche, S. and Roux, B.  Energetics of ion conduction through the K= channel.
        Nature 414, 73-77 (2001).

 

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