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Structure of the human cation-chloride cotransporter NKCC1 determined by single-particle electron cryo-microscopy.

Nature communications (2020-02-23)
Xiaoyong Yang, Qinzhe Wang, Erhu Cao
ABSTRACT

The secondary active cation-chloride cotransporters (CCCs) utilize the existing Na+ and/or K+ gradients to move Cl- into or out of cells. NKCC1 is an intensively studied member of the CCC family and plays fundamental roles in regulating trans-epithelial ion movement, cell volume, chloride homeostasis and neuronal excitability. Here, we report a cryo-EM structure of human NKCC1 captured in a partially loaded, inward-open state. NKCC1 assembles into a dimer, with the first ten transmembrane (TM) helices harboring the transport core and TM11-TM12 helices lining the dimer interface. TM1 and TM6 helices break α-helical geometry halfway across the lipid bilayer where ion binding sites are organized around these discontinuous regions. NKCC1 may harbor multiple extracellular entryways and intracellular exits, raising the possibility that K+, Na+, and Cl- ions may traverse along their own routes for translocation. NKCC1 structure provides a blueprint for further probing structure-function relationships of NKCC1 and other CCCs.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Maltose solution, BioReagent, for molecular biology, ~20% in H2O
Sigma-Aldrich
Anti-SLC12A2 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution