PUBLICATION
The cryo-EM structures of DrNKCC1 and hKCC1: a new milestone in the physiology of cation-chloride cotransporters
- Authors
- Delpire, E., Guo, J.
- ID
- ZDB-PUB-191121-11
- Date
- 2019
- Source
- American journal of physiology. Cell physiology 318(2): C225-C237 (Review)
- Registered Authors
- Keywords
- K-Cl cotransporter, Na-K-2Cl cotransporter, ion binding, rapid equilibrium, transport kinetics
- MeSH Terms
-
- Animals
- Cations/chemistry*
- Chlorides/chemistry*
- Amino Acid Sequence
- Solute Carrier Family 12, Member 2/chemistry*
- Symporters/chemistry*
- Humans
- Cryoelectron Microscopy/methods
- PubMed
- 31747317 Full text @ Am. J. Physiol. Cell Physiol.
Citation
Delpire, E., Guo, J. (2019) The cryo-EM structures of DrNKCC1 and hKCC1: a new milestone in the physiology of cation-chloride cotransporters. American journal of physiology. Cell physiology. 318(2):C225-C237.
Abstract
New milestones have been crossed in the field of cation-chloride cotransporters with the recently released cryo-electron microscopy structures of the Danio rerio (zebrafish) NKCC1 and human KCC1 cotransporters. In this review, we provide a brief timeline that identifies the multiple breakthroughs that were made in the field of solute carrier 12 (SLC12) transporters and that led to the structure resolution of two of its key members. While cation-chloride cotransporters share the overall architecture of carriers belonging to the amino acid, polyamine, organocation (APC) superfamily and some of their substrate binding sites, several new insights are gained from the two individual structures. A first major feature relates to the largest extracellular domain between transmembrane domains 5 and 6 of KCC1 which stabilizes the dimer and forms a cap that likely participates in extracellular gating. A second feature is the conservation of the potassium (K+) and chloride (Cl-) binding sites in both structures, and evidence of an unexpected second Cl- coordination site in the KCC1 structure. Structural data are discussed in the context of previously published studies that examined the basic and kinetics properties of these cotransport mechanisms. A third characteristic is the evidence of an extracellular gate formed by conserved salt bridges between charged residues located towards the end of transmembrane domains 3 and 4 in both transporters, and the existence of an additional neighboring bridge in the hKCC1 structure. A fourth feature of these newly solved structures relates to the multiple points of contacts that exist between the monomer forming the cotransporter homodimer units. These involve the transmembrane domains, the carboxyl-terminal domains, and the large extracellular loop for hKCC1.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping