6UKN
Cryo-EM structure of the potassium-chloride cotransporter KCC4 in lipid nanodiscs
Summary for 6UKN
| Entry DOI | 10.2210/pdb6ukn/pdb |
| EMDB information | 20807 |
| Descriptor | Solute carrier family 12 member 7, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, POTASSIUM ION, ... (4 entities in total) |
| Functional Keywords | potassium chloride cotransporter, slc12, transport protein |
| Biological source | Mus musculus (Mouse) |
| Total number of polymer chains | 1 |
| Total formula weight | 121858.60 |
| Authors | Reid, M.S.,Kern, D.M.,Brohawn, S.G. (deposition date: 2019-10-05, release date: 2020-06-10, Last modification date: 2024-10-23) |
| Primary citation | Reid, M.S.,Kern, D.M.,Brohawn, S.G. Cryo-EM structure of the potassium-chloride cotransporter KCC4 in lipid nanodiscs. Elife, 9:-, 2020 Cited by PubMed Abstract: Cation-chloride-cotransporters (CCCs) catalyze transport of Cl with K and/or Naacross 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 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. PubMed: 32286222DOI: 10.7554/eLife.52505 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.65 Å) |
Structure validation
Download full validation report
