Davies, James S. and Zeng, Yi C. and Briot, Chelsea and Brown, Simon H. J. and Ryan, Renae M. and Stewart, Alastair G. (2025) Structural basis of sodium ion-dependent carnitine transport by OCTN2. Nature Communications, 17 (1). ISSN 2041-1723
Full text not available from this repository.Abstract
Abstract
Carnitine is essential for the import of long-chain fatty acids into mitochondria, where they are used for energy production. The carnitine transporter OCTN2 (novel organic cation transporter 2, SLC22A5) mediates carnitine uptake across the plasma membrane and as such facilitates fatty acid metabolism in most tissues. OCTN2 dysfunction causes systemic primary carnitine deficiency (SPCD), a potentially lethal disorder. Despite its importance in metabolism, the mechanism of high-affinity, sodium ion-dependent transport by OCTN2 is unclear. Here we report cryo-EM structures of human OCTN2 in three conformations: inward-facing ligand-free, occluded carnitine- and Na + -bound, and inward-facing ipratropium-bound. These structures define key interactions responsible for carnitine transport and identify an allosterically coupled Na + binding site housed within an aqueous cavity, separate from the carnitine-binding site. Combined with electrophysiology data, we provide a framework for understanding variants associated with SPCD and insight into how OCTN2 functions as the primary human carnitine transporter.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 04 Sep 2026 06:14 |
| Last Modified: | 04 Sep 2026 06:14 |
| URI: | http://eprints.victorchang.edu.au/id/eprint/1836 |
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