Correlation Engine 2.0
Clear Search sequence regions

  • across (1)
  • cation (5)
  • cellular (2)
  • insight (1)
  • ion transport (1)
  • ions (1)
  • KCC4 (3)
  • lipid (3)
  • loop diuretics (1)
  • mice (1)
  • mus musculus (1)
  • potassium (1)
  • renal function (1)
  • Sizes of these terms reflect their relevance to your search.

    Cation-chloride-cotransporters (CCCs) catalyze transport of Cl- with K+ and/or Na+across cellular membranes. CCCs play roles in cellular volume regulation, neural development and function, audition, regulation of blood pressure, and renal function. CCCs are targets of clinically important drugs including loop diuretics and their disruption has been implicated in pathophysiology including epilepsy, hearing loss, and the genetic disorders Andermann, Gitelman, and Bartter syndromes. Here we present the structure of a CCC, the Mus musculus K+-Cl- cotransporter (KCC) KCC4, in lipid nanodiscs determined by cryo-EM. The structure, captured in an inside-open conformation, reveals the architecture of KCCs including an extracellular domain poised to regulate transport activity through an outer gate. We identify binding sites for substrate K+ and Cl- ions, demonstrate the importance of key coordinating residues for transporter activity, and provide a structural explanation for varied substrate specificity and ion transport ratio among CCCs. These results provide mechanistic insight into the function and regulation of a physiologically important transporter family. © 2020, Reid et al.


    Michelle S Reid, David M Kern, Stephen Graf Brohawn. Cryo-EM structure of the potassium-chloride cotransporter KCC4 in lipid nanodiscs. eLife. 2020 Apr 14;9

    Expand section icon Mesh Tags

    Expand section icon Substances

    PMID: 32286222

    View Full Text