Membrane permeation is achieved by a variety of mechanisms

LeuT Na + -dependent pump KcsA K + channel Ca 2+ ATPase pump ClC Cl – /H + exchanger The number of binding sites varies

Ion binding correlated with protein conformational changes in a K + channel and a Ca 2+ pump.

The Structure of the Calcium Channel: Basis of Ca 2+ Conduction and Selectivity Sather and McCleskey (2003), Ann Review Phys

Membrane topology and amino acid sequences that form part of the pore lining for a cardiac L-type Ca channel.

Quadruple mutants of the EEEE locus lack high-affinity binding of divalent cations.

Fanciful depiction of hypothesized structural flexibility in the EEEE locus.

Three Ca 2+ ions (violet balls) bound to the EEEE locus.

The Structure of the Potassium Channel: Molecular Basis of K+ Conduction and Selectivity Mackinnon et al.

potassium channels permeability and specificity homology of structure

previous research revealing the pore K+ channel signature sequence figure 1

targeting the subunit figure 4 white yellow mustard green pink red

revealing the subunit Michael Andrew Meyer, MD From Neuron to Brain (4th Edition, Sinauer Associates) figure 2 A & B

the subunit grasp: tetrameric figure 3 A & B

x-ray crystallography Long et al figure 3C

the selectivity / permeability paradox

complementation and passage minimize length of crossing encourage those who wish to cross figure 5 A & B

hold their hands and invite them in figure 7 figure 3D

specific stabilization figure 8C figure 6