9PMD

Human OCTN2 in an inward-facing conformation

9PMD の概要

• エントリーDOI: 10.2210/pdb9pmd/pdb
• 関連するPDBエントリー: 9PDQ 9PFB
• EMDBエントリー: 71735
• 分子名称: Organic cation/carnitine transporter 2, SODIUM ION (3 entities in total)
• 機能のキーワード: transporter, carnitine transporter, organic cation transporter, slc22 family, sodium-dependent transport, membrane protein, solute carrier, metabolic transport, fatty acid oxidation, octn2, slc22a5, transport protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 64275.97

構造登録者

Davies, J.S.,Zeng, Y.Z.,Stewart, A.G. (登録日: 2025-07-17, 公開日: 2025-12-03, 最終更新日: 2026-01-21)

主引用文献

Davies, J.S.,Zeng, Y.C.,Briot, C.,Brown, S.H.J.,Ryan, R.M.,Stewart, A.G.
Structural basis of sodium ion-dependent carnitine transport by OCTN2.
Nat Commun, 17:181-181, 2025

PubMed 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.

PubMed: 41318751
DOI: 10.1038/s41467-025-66867-6

実験手法

ELECTRON MICROSCOPY (2.99 Å)