Membrane permeation is achieved by a variety of mechanisms

LeuT Na+-dependent pump KcsA K+ channel

Ca2+ 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 Ca2+ pump.

The Structure of the Calcium Channel: Basis of Ca2+

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 Ca2+ ions (violet balls) bound to the EEEE locus.

The Structure of the Potassium Channel: Molecular Basis of K+

Conduction and SelectivityMackinnon et al.

potassium channelspermeability

and specificity

homology of structure

previous research

revealing the pore

K+ channel signature sequence

figure 1

targeting the subunitfigure 4

whitewhite

yellow

mustard

green

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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. 2005

figure 3C

the selectivity / permeability paradox

complementation and passageminimize 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