Cation Chloride Cotransporter NKCC1 Operates through a Rocking-Bundle Mechanism.

ABSTRACT: The sodium, potassium, and chloride cotransporter 1 (NKCC1) plays a key role in tightly regulating ion shuttling across cell membranes. Lately, its aberrant expression and function have been linked to numerous neurological disorders and cancers, making it a novel and highly promising pharmacological target for therapeutic interventions. A better understanding of how NKCC1 dynamically operates would therefore have broad implications for ongoing efforts toward its exploitation as a therapeutic target through its modulation. Based on recent structural data on NKCC1, we reveal conformational motions that are key to its function. Using extensive deep-learning-guided atomistic simulations of NKCC1 models embedded into the membrane, we captured complex dynamical transitions between alternate open

SUBMITTER: Ruiz Munevar MJ 

PROVIDER: S-EPMC10786066 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature