6KKU

human KCC1 structure determined in NaCl and GDN

Summary for 6KKU

• Entry DOI: 10.2210/pdb6kku/pdb
• EMDB information: 0701 0702 0703
• Related PRD ID: PRD_900018
• Descriptor: Solute carrier family 12 member 4, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-glucopyranose-(1-4)-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: ion co-transporter, transport protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 248280.95

Authors

Liu, S.,Chang, S.,Ye, S.,Bai, X.,Guo, J. (deposition date: 2019-07-27, release date: 2019-10-23, Last modification date: 2024-11-20)

Primary citation

Liu, S.,Chang, S.,Han, B.,Xu, L.,Zhang, M.,Zhao, C.,Yang, W.,Wang, F.,Li, J.,Delpire, E.,Ye, S.,Bai, X.C.,Guo, J.
Cryo-EM structures of the human cation-chloride cotransporter KCC1.
Science, 366:505-508, 2019

PubMed Abstract: Cation-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 γ-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.

PubMed: 31649201
DOI: 10.1126/science.aay3129

Experimental method

ELECTRON MICROSCOPY (3.5 Å)