Week 4b: Ion channel structure BIOL3833 Week 4b: Ion channel structure

Game plan for today: 12:00 to ~12:30 Lecture: Ion channel structure 12:30-1:15 Complete simulation experiments

Structural properties of ion channels: Membrane spanning proteins that allow: Selective permeability Rapid ion movement Gating (by voltage or ligands) Inactivation mechanism (only some channels) Modulation (fast/slow changes in voltage dependence or kinetics)

Proteins are made of these:

This is an ion channel: Well, actually this is 1/4th of an ion channel

Voltage-gated K+ channel: 6 Transmembrane segments 1 Subunit Pore region 4 subunits form channel Need 20 AA to span membrane

Voltage-gated Na+ channel: Four domains in ONE subunit Pore region IFM “inactivation loop”

Selectivity filter in the pore Mystery: K+ ions are larger than Na+ ions Hydrated Na+ ions larger than hydrated K+ ions How do sodium and potassium channels select?

Water is a polar molecule

Ion movement is way fast How does the channel select for only one type of ion, while still allowing them to move at a rate approaching unrestricted free diffusion?

How? How can it be selective and fast? Rod MacKinnon figured it out: http://www.nobelprize.org/mediaplayer/index.php?id=550 Start Video at 15:15 End at 24:00

Béla

Choe (2002) Nat Rev Neurosci

S5 S6 http://www.ks.uiuc.edu/Research/kvchannel/

Mechanism of voltage-gating

Mechanism of voltage-gating

Mechanism of inactivation

Modulation of channel function

Structural properties of ion channels produce: Membrane spanning proteins that allow: Selective permeability Rapid ion movement Gating (by voltage or ligands) Inactivation mechanism (only some channels) Modulation (function can be rapidly changed)

Ion channels are very finely tuned: Small mutations cause disease states