6kkt
human KCC1 structure determined in KCl and lipid nanodisc
Structural highlights
FunctionS12A4_HUMAN Mediates electroneutral potassium-chloride cotransport when activated by cell swelling. May contribute to cell volume homeostasis in single cells. May be involved in the regulation of basolateral Cl(-) exit in NaCl absorbing epithelia (By similarity). Isoform 4 has no transport activity. Publication Abstract from PubMedCation-chloride cotransporters (CCCs) mediate the coupled, electroneutral symport of cations with chloride across the plasma membrane and are vital for cell volume regulation, salt reabsorption in the kidney, and gamma-aminobutyric acid (GABA)-mediated modulation in neurons. Here we present cryo-electron microscopy (cryo-EM) structures of human potassium-chloride cotransporter KCC1 in potassium chloride or sodium chloride at 2.9- to 3.5-angstrom resolution. KCC1 exists as a dimer, with both extracellular and transmembrane domains involved in dimerization. The structural and functional analyses, along with computational studies, reveal one potassium site and two chloride sites in KCC1, which are all required for the ion transport activity. KCC1 adopts an inward-facing conformation, with the extracellular gate occluded. The KCC1 structures allow us to model a potential ion transport mechanism in KCCs and provide a blueprint for drug design. Cryo-EM structures of the human cation-chloride cotransporter KCC1.,Liu S, Chang S, Han B, Xu L, Zhang M, Zhao C, Yang W, Wang F, Li J, Delpire E, Ye S, Bai XC, Guo J Science. 2019 Oct 25;366(6464):505-508. doi: 10.1126/science.aay3129. PMID:31649201[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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