Structure of a Eukaryotic CLC Transporter Defines an Intermediate State in the Transport Cycle

摘要: CLC proteins transport chloride (Cl(-)) ions across cell membranes to control the electrical potential of muscle cells, transfer electrolytes epithelia, and pH electrolyte composition intracellular organelles. Some members this protein family are Cl(-) ion channels, whereas others secondary active transporters that exchange protons (H(+)) with a 2:1 stoichiometry. We have determined structure eukaryotic transporter at 3.5 angstrom resolution. Cytoplasmic cystathionine beta-synthase (CBS) domains strategically positioned regulate ion-transport pathway, many disease-causing mutations in human CLCs reside on CBS-transmembrane interface. Comparison prokaryotic shows gating glutamate residue changes conformation suggests basis for Cl(-)/H(+) simple mechanistic connection between channels transporters.