Structure and mechanism of the cation-chloride cotransporter NKCC1.
Nature
; 572(7770): 488-492, 2019 08.
Article
em En
| MEDLINE
| ID: mdl-31367042
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peixe-Zebra
/
Microscopia Crioeletrônica
/
Membro 2 da Família 12 de Carreador de Soluto
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nature
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos