Structure of a Eukaryotic CLC Transporter Defines an Intermediate State in the Transport Cycle
- Rockefeller
CLC proteins transport chloride (Cl{sup -}) ions across cell membranes to control the electrical potential of muscle cells, transfer electrolytes across epithelia, and control the pH and electrolyte composition of intracellular organelles. Some members of this protein family are Cl{sup -} ion channels, whereas others are secondary active transporters that exchange Cl{sup -} ions and protons (H{sup +}) with a 2:1 stoichiometry. We have determined the structure of a eukaryotic CLC transporter at 3.5 angstrom resolution. Cytoplasmic cystathionine beta-synthase (CBS) domains are strategically positioned to regulate the ion-transport pathway, and many disease-causing mutations in human CLCs reside on the CBS-transmembrane interface. Comparison with prokaryotic CLC shows that a gating glutamate residue changes conformation and suggests a basis for 2:1 Cl{sup -}/H{sup +} exchange and a simple mechanistic connection between CLC channels and transporters.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 1002878
- Journal Information:
- Science, Vol. 330, Issue 10, 2010; ISSN 0193-4511
- Country of Publication:
- United States
- Language:
- ENGLISH
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