Structure of the human cation-chloride cotransport KCC1 in an outward-open state.

ABSTRACT: Cation-chloride cotransporters (CCCs) catalyze electroneutral symport of Cl^- with Na⁺ and/or K⁺ across membranes. CCCs are fundamental in cell volume homeostasis, transepithelia ion movement, maintenance of intracellular Cl^- concentration, and neuronal excitability. Here, we present a cryoelectron microscopy structure of human K⁺-Cl^- cotransporter (KCC)1 bound with the VU0463271 inhibitor in an outward-open state. In contrast to many other amino acid-polyamine-organocation transporter cousins, our first outward-open CCC structure reveals that opening the KCC1 extracellular ion permeation path does not involve hinge-bending motions of the transmembrane (TM) 1 and TM6 half-helices. Instead, rocking of TM3 and TM8, together wit

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC9271165 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature