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Structure paper

TitleStructure and mechanism of the cation-chloride cotransporter NKCC1.
Journal, issue, pagesNature, Vol. 572, Issue 7770, Page 488-492, Year 2019
Publish dateJul 31, 2019
AuthorsThomas A Chew / Benjamin J Orlando / Jinru Zhang / Naomi R Latorraca / Amy Wang / Scott A Hollingsworth / Dong-Hua Chen / Ron O Dror / Maofu Liao / Liang Feng /
PubMed AbstractCation-chloride cotransporters (CCCs) mediate the electroneutral transport of chloride, potassium and/or sodium across the membrane. They have critical roles in regulating cell volume, controlling ...Cation-chloride cotransporters (CCCs) mediate the electroneutral transport of chloride, potassium and/or sodium across the membrane. They have critical roles in regulating cell volume, controlling ion absorption and secretion across epithelia, and maintaining intracellular chloride homeostasis. These transporters are primary targets for some of the most commonly prescribed drugs. Here we determined the cryo-electron microscopy structure of the Na-K-Cl cotransporter NKCC1, an extensively studied member of the CCC family, from Danio rerio. The structure defines the architecture of this protein family and reveals how cytosolic and transmembrane domains are strategically positioned for communication. Structural analyses, functional characterizations and computational studies reveal the ion-translocation pathway, ion-binding sites and key residues for transport activity. These results provide insights into ion selectivity, coupling and translocation, and establish a framework for understanding the physiological functions of CCCs and interpreting disease-related mutations.
External linksNature / PubMed:31367042 / PubMed Central
MethodsEM (single particle)
Resolution2.9 - 4.2 Å
Structure data

EMDB-0470, PDB-6nph:
Structure of NKCC1 TM domain
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-0471, PDB-6npj:
Structure of the NKCC1 CTD
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-0472, PDB-6npk:
Structure of the TM domain
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-0473, PDB-6npl:
Cryo-EM structure of NKCC1
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-0474:
cryoEM map of NKCC1
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-0475:
cryoEM map of NKCC1
Method: EM (single particle) / Resolution: 4.2 Å

Chemicals

ChemComp-POV:
(2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipid*YM / POPC

ChemComp-K:
Unknown entry

ChemComp-CL:
Unknown entry / Chloride

Source
  • danio rerio (zebrafish)
  • Spodoptera frugiperda (fall armyworm)
KeywordsMEMBRANE PROTEIN

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