EMD-14709

Single-particle
2.55 Å
EMD-14709 Deposition: 04/04/2022
Map released: 05/10/2022
Last modified: 20/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-14709

Cryo-EM structure of human NKCC1 (TM domain)

EMD-14709

Single-particle
2.55 Å
EMD-14709 Deposition: 04/04/2022
Map released: 05/10/2022
Last modified: 20/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: Dimeric NKCC1 in complex with Na+, K+ and 2Cl-
Fitted models: 7zgo (Avg. Q-score: 0.576)

Deposition Authors: Nissen P , Fenton R , Neumann C , Lindtoft Rosenbaek L, Kock Flygaard R , Habeck M , Lykkegaard Karlsen J , Wang Y , Lindorff-Larsen K , Gad H , Hartmann R , Lyons J
Cryo-EM structure of the human NKCC1 transporter reveals mechanisms of ion coupling and specificity.
PUBMED: 36239040
DOI: doi:10.15252/embj.2021110169
ISSN: 1460-2075
ASTM: EMJODG
Abstract:
The sodium-potassium-chloride transporter NKCC1 of the SLC12 family performs Na+ -dependent Cl- - and K+ -ion uptake across plasma membranes. NKCC1 is important for regulating cell volume, hearing, blood pressure, and regulation of hyperpolarizing GABAergic and glycinergic signaling in the central nervous system. Here, we present a 2.6 Å resolution cryo-electron microscopy structure of human NKCC1 in the substrate-loaded (Na+ , K+ , and 2 Cl- ) and occluded, inward-facing state that has also been observed for the SLC6-type transporters MhsT and LeuT. Cl- binding at the Cl1 site together with the nearby K+ ion provides a crucial bridge between the LeuT-fold scaffold and bundle domains. Cl- -ion binding at the Cl2 site seems to undertake a structural role similar to conserved glutamate of SLC6 transporters and may allow for Cl- -sensitive regulation of transport. Supported by functional studies in mammalian cells and computational simulations, we describe a putative Na+ release pathway along transmembrane helix 5 coupled to the Cl2 site. The results provide insight into the structure-function relationship of NKCC1 with broader implications for other SLC12 family members.