June 4, 2010 | David F. Coppedge

Your Nerves and Heart Depend on Cellular Pulleys, Latches and Switches

Biologists continue to peer closer and closer at cellular machines that work just like man-made ones, only at scales so tiny, they control individual atoms.  Of particular interest have been the gates in the membranes of cells that allow certain atoms in but keep others out.  A recent paper in Cell by an Australian team has found that the potassium gate has an elegant switch that uses pulleys, switches and an iris-like rotating latch that selectively lets in potassium ions.1
    Your heart and central nervous system (CNS) rely on potassium (K) to set up electrical charges in nerve cells.  These charges travel down nerves to carry messages, or, in the case of the heart, set up the electrical oscillations necessary to keep the heart active.  How do the gates let in potassium ions but keep sodium (Na) ions out, which are 8 atomic mass units lighter?
    Many groups have studied the potassium channels for years (e.g., 01/17/2002, 03/12/2002).  The gate consists of four primary parts fitted together to form a channel, with a “selectivity filter” that ensures only potassium ions get through.  The Australian team studied a particular potassium gate, the Kir channel, and found several mechanical actions at work:

  • Latches:  “Intersubunit connections are clustered near the membrane in the latched arrangement, but they reorganize, in the unlatched arrangement, into a more extensive array of interactions.”
  • Irises:  “The net effect of staged unlatching at all four interfaces (structures VI?VIII) is a symmetrical iris-like dilation of a narrow opening to the intracellular vestibule by approximately 4.5 ? relative to I (Figure 1G), extending the permeation pore through both domains (Movie S2).”
  • Pulleys:  “Coupling is facilitated by actions of the N and C termini, which effectively act as a pulley system.  The intracellular domain of each subunit is an immunoglobulin-like [beta] sandwich, overlaid on the surface by N and C termini.  Its C terminus is tethered both to the N terminus and the underlying [beta] sandwich such that all motions are interdependent.  In addition, parallel [beta] sheet interactions formed between [beta]CN on one subunit and [beta]M on another (Figure 3D) adapt the basic fold by interweaving neighboring subunits into a circle, coupling the motion of each subunit to that of its neighbor.
  • Switches:  “Our findings provide strong evidence that the selectivity filter can switch between nonconducting and conducting configurations without significant displacement of the inner helices.  This is distinct from findings that inactivation at the selectivity filter is driven by widening at the bundle crossing, and vice versa ([Blunck et al., 2006] and [Cordero-Morales et al., 2007]).  While research into selectivity filter gating has primarily focused on C-type inactivation, our data indicate that the selectivity filter is not limited to this and is susceptible to subtle global conformational change, suggesting a more universal role in gating than hitherto expected.
  • Rotors:  “The structures cluster into two groups with distinct conformations, independent of space group and crystal form.  The difference between the groups corresponds to a rigid body rotation of 23° (viewed from the membrane), about the molecular four-fold, of the entire intracellular assembly relative to the transmembrane pore (Figure 1C) (Movie S1).”

All of these mechanical actions are coordinated and “global,” they said.  One subsection of the paper was titled, “Ion Configuration Is Linked to the Global Conformation of the Channel,” and another, “Twisting: Global Conformation Is Correlated to Slide Helix Orientation.”  Indeed, “global” was a characteristic word in the paper: “A major finding is that the number and site distribution of bound ions in the selectivity filter are contingent on global conformational changes.2  The paper included animations showing how these twisting, bending, latching, and pulling motions all work together so that the right ions get through and the wrong ones do not.  The entire gate switches between a conducting state and a nonconducting state in response to environmental cues, just like an automated turnstile or drawbridge system on a vastly different scale.
    For a short summary of this paper, see Science DailyPhysOrg reprinted the 5-minute movie from the paper by Gulbis and Clarke that explains their main findings and shows animations of the Kir potassium gate in action.  At the 2:20 point in the movie, one can see the 23° rotation of the bottom subunit.  At the 3:25 point, one can see some of the global conformational changes (switches, latches and pulleys) that operate the channel mechanism.  The viewer should keep in mind that in real life these actions occur extremely rapidly.  The Kir channel can selectively pass millions of potassium ions per second while keeping out interlopers.  Because of voltage-gated channels such as these, neurons can transmit up to a thousand impulses per second at speeds of 120 meters per second.

1.  Clark, Caputo, Hill, Vandenburg, Smith and Gulbis, “Domain Reorientation and Rotation of an Intracellular Assembly Regulate Conduction in Kir Potassium Channels,” Cell, June 3, 2010 DOI: 10.1016/j.cell.2010.05.003.
2.  Molecular biologists use the phrase conformational change to refer to any physical reorganization of the domains of a protein or cellular molecular, such as a twist, rotation, bend, or fold of some parts relative to others.  It is comparable to the actions of machinery with moving parts.

There was no mention of evolution in this paper.  The only oblique references to evolution at all were six statements that some amino acids were “conserved” (i.e., unevolved) in various positions of the channel, two of which were “highly conserved.”  OK, great – Darwin need not apply.  Here are molecules doing physical work, at a precision level, with exquisitely beautiful function, absolutely essential to life, all the way from bacteria (03/12/2002) to man.  The elegance and sophistication of these gates is astounding.  Of what possible benefit is evolutionary theory here?  Where does it help to elucidate the structure of these gates or to help us understand their origin?  On the contrary; it is by intelligent design that we sense design, we find design, we understand design, we reverse-engineer design, and we apply design.  We can look at the design of these gates and learn something.  The design we find in living things works so well, it can motivate scientists to design better artificial devices.  It’s ID science through and through.
    Take a moment next time you feel a pleasant sensation – whether from good food, sex, a warm cup of coffee, a gentle breeze on the skin, the tightness of a well-exercised muscle, a beautiful view, wonderful music, a loving hug – to ponder that those feelings don’t just happen.  Those active sensations (and many more passive signals in the autonomic nervous system) are mediated through trillions of exquisitely crafted potassium channel machines.  They work throughout your life without your conscious thought.  This brings us to another benefit of design-based science.  Understanding the intricacy of these structures, that work so efficiently at this incredibly tiny scale, leads to awe.  Awe leads to humility.  Humility leads to worship.  Worship leads to unselfishness.  Unselfishness leads to altruism.  Couldn’t the world use a little more of those spin-offs?
    Thanks to Brett Miller for another new donated illustration for “Amazing Facts” entries in Creation-Evolution Headlines.  Watch for this symbol and another new one in forthcoming articles.  His website is EvidentCreation.com, where you can find articles and a collection of his clever and thought-provoking cartoons.

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