CLC Chloride Channel

In vertebrates the CLC chloride channel serves several important functions.  In skeletal muscles this channel stabilizes the resting membrane potential and regulates electrical excitability.  In the kidney this channel helps produce transepithelial fluid and electrolyte transport. 

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Original Settings (the top part of the channel is the extracellular region where the concentration of chloride ions is high.  The bottom is the intracelluar region)

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Quaternary Structure

Cartoon Model (a total of 18 alpha helices)

Cartoon and Wire Frame

Mixed Rendering

Ribbon View

Chloride Channel Subunits

Consisting of two identical pores,  the antiparallel architecture creates two individual selectivity filters that stabilizes the chloride ion by electrostatic interactions with the alpha-helix dipoles and by coordination with nitrogen atoms and hydroxyl groups.  Each subunit is triangular with a large interface which would be expected because the chloride channels are only thought to exist as dimers. 

Original Settings

One Subunit

Wire Frame - Subunits

Cartoon Model - Subunits

Chloride Binding Site (the favorable electrostatic environment for chloride comes not from positive charges of arginine or lysine but from the partial positive charges of helix dipole interactions and by contacts with main-chain nitrogen and oxygen atoms.  A full positive charge would cause the chloride ion to bind too tightly.)

Original Settings

Chloride Ions

Backbone - Ion Binding Site (located at the N termini of alpha-helices and a strong peak of electron density)

Wire Frame - Ion Binding Site

Cartoon - Ion Binding Site

Space Fill - Ion Binding Site

Original Settings

Ser 107 and Tyr 445 coordinate the chloride ion by side-chain oxygen atoms.  Because of its aromatic ring, Tyr is an excellent proton donor.

Ile356 and Phe357coordinate the chloride ion by main-chain chain nitrogen atoms

Other Chloride ion Coordinators

Chloride ion coordinators-space fill

Ion Binding Site

Regions of CLC Chloride Channel

Charged regions the transmembrane region is devoid of charges

Acidic regions

Basic regions

Original Settings

Electrostatic surface potential (the two areas in blue are the extracellular entryways of the chloride ion)  Wait to load.

Rotate 90 on X axis

Molecular lipophilicity surface potential  Wait to load

 

 

Created by Laura Nezworski and Monica Hurtubise