9PFB
Human OCTN2 bound to ipratropium in an inward-facing conformation
Summary for 9PFB
| Entry DOI | 10.2210/pdb9pfb/pdb |
| Related | 9PDQ |
| EMDB information | 71597 |
| Descriptor | Organic cation/carnitine transporter 2, IPRATROPIUM, SODIUM ION (3 entities in total) |
| Functional Keywords | transporter, carnitine transporter, organic cation transporter, slc22 family, sodium-dependent transport, membrane protein, solute carrier, metabolic transport, fatty acid oxidation, octn2, slc22a5, ipratropium, inhibitor, transport protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 64608.42 |
| Authors | Davies, J.S.,Zeng, Y.Z.,Stewart, A.G. (deposition date: 2025-07-03, release date: 2025-12-03, Last modification date: 2026-01-21) |
| Primary citation | 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 Cited by 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: 41318751DOI: 10.1038/s41467-025-66867-6 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.06 Å) |
Structure validation
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