Structure and mechanism of the cation–chloride cotransporter NKCC1

Thomas A. Chew, Benjamin J. Orlando, Jinru Zhang, Naomi R. Latorraca, Amy Wang, Scott A. Hollingsworth, Dong-Hua Chen, Ron O. Dror, Maofu Liao () and Liang Feng ()
Additional contact information
Thomas A. Chew: Stanford University School of Medicine
Benjamin J. Orlando: Harvard Medical School
Jinru Zhang: Stanford University School of Medicine
Naomi R. Latorraca: Stanford University School of Medicine
Amy Wang: Stanford University School of Medicine
Scott A. Hollingsworth: Stanford University School of Medicine
Dong-Hua Chen: Stanford University School of Medicine
Ron O. Dror: Stanford University School of Medicine
Maofu Liao: Harvard Medical School
Liang Feng: Stanford University School of Medicine

Nature, 2019, vol. 572, issue 7770, 488-492

Abstract: Abstract 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.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41586-019-1438-2 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:572:y:2019:i:7770:d:10.1038_s41586-019-1438-2

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-019-1438-2

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().