6ukn

Cryo-EM structure of the potassium-chloride cotransporter KCC4 in lipid nanodiscs

spinqualitylabelsall models 6ukn, resolution 3.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.65Å Ligands: BMA, CL, K, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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. Cryo-EM structure of the potassium-chloride cotransporter KCC4 in lipid nanodiscs.,Reid MS, Kern DM, Brohawn SG Elife. 2020 Apr 14;9. pii: 52505. doi: 10.7554/eLife.52505. PMID:32286222 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Solute carrier family 12 3D structures Symporter 3D structures

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