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TitleCryo-EM structures of the human cation-chloride cotransporter KCC1.
Journal, issue, pagesScience, Vol. 366, Issue 6464, Page 505-508, Year 2019
Publish dateOct 25, 2019
AuthorsSi Liu / Shenghai Chang / Binming Han / Lingyi Xu / Mingfeng Zhang / Cheng Zhao / Wei Yang / Feng Wang / Jingyuan Li / Eric Delpire / Sheng Ye / Xiao-Chen Bai / Jiangtao Guo /
PubMed AbstractCation-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 ...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.
External linksScience / PubMed:31649201
MethodsEM (single particle)
Resolution2.9 - 3.5 Å
Structure data

0701

6kkr

EMDB-0701, PDB-6kkr:
human KCC1 structure determined in KCl and detergent GDN
Method: EM (single particle) / Resolution: 2.9 Å

0702

6kkt

EMDB-0702, PDB-6kkt:
human KCC1 structure determined in KCl and lipid nanodisc
Method: EM (single particle) / Resolution: 2.9 Å

0703

6kku

EMDB-0703, PDB-6kku:
human KCC1 structure determined in NaCl and GDN
Method: EM (single particle) / Resolution: 3.5 Å

Chemicals

ChemComp-CL:
Unknown entry

ChemComp-K:
Unknown entry

ChemComp-DU0:
2-[2-[(1~{S},2~{S},4~{S},5'~{R},6~{R},7~{S},8~{R},9~{S},12~{S},13~{R},16~{S})-5',7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icos-18-ene-6,2'-oxane]-16-yl]oxyethyl]propane-1,3-diol

Source
  • homo sapiens (human)
KeywordsTRANSPORT PROTEIN / ion co-transporter

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