CLC Chloride Channel

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Introduction

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.

For more information see Biochemistry Online: Chapter 9B - Signal Transduction: Neurochemistry

Wire Frame

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

Quaternary Structure (2 subunits)

Backbone
Cartoon showing hydrogen bonds (a total of 18 alpha helices)
Cartoon and Wireframe

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.

One Subunit
Both Subunits
Both Subunits in carton

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.

Backbone - Cl Ion Binding Site (located at the N termini of alpha-helices and a strong peak of electron density)
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 Phe357 coordinate the chloride ion by main-chain chain nitrogen atoms
Other Chloride ion Coordinators
Ion Binding Site