9SQH
Cryo-EM structure of the Arabidopsis thaliana CAT4 transporter in the outward-open apo state (without synthetic nanobody)
Summary for 9SQH
| Entry DOI | 10.2210/pdb9sqh/pdb |
| EMDB information | 55110 |
| Descriptor | Cationic amino acid transporter 4, vacuolar (1 entity in total) |
| Functional Keywords | cationic amino acid transporter, apc fold, leut fold, cholesterol, outward-open state, cationic amino acids, slc7, membrane protein, transport protein |
| Biological source | Arabidopsis thaliana (thale cress) |
| Total number of polymer chains | 1 |
| Total formula weight | 63680.15 |
| Authors | |
| Primary citation | Kolokouris, D.,Bothra, A.,Kato, T.,Zeng, Y.C.,Lichtinger, S.,Parker, J.L.,Biggin, P.C.,Newstead, S. Structural basis for pH-responsive amino acid transport via SLC7A4. Nat Commun, 2026 Cited by PubMed Abstract: The transport of amino acids across cell membranes is essential for metabolism, neuronal signalling, and immune system function. The amino acid polyamine organocation (APC) superfamily controls amino acid transport via mechanisms including amino acid exchange, facilitative diffusion, and sodium- or proton-coupled transport. Although many mammalian APC members functioning as exchangers and sodium-coupled systems have been identified, the mechanisms underlying pH-regulated amino acid transport in mammalian cells remain unclear. Here, we show that the plasma membrane amino acid transporter SLC7A4 is regulated by low extracellular pH and functions as a leucine transporter in human cells. Using Cryo-EM structures of the plant homologue, CAT4, from Arabidopsis thaliana in outward-open apo and L-ornithine-bound states, as well as transport assays and molecular dynamics simulations based on homology models of the human transporter, we identify residues responsible for amino acid selectivity that supports an allosteric mechanism linking ligand recognition to pH regulation. This mechanism is consistent with an evolutionary link to proton-coupled prokaryotic homologues. Overall, our findings provide a structural and functional basis for pH-gated leucine transport by the human SLC7A4 transporter and provides a framework for understanding amino acid selectivity within the wider SLC7 family. PubMed: 41904136DOI: 10.1038/s41467-026-70956-5 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.23 Å) |
Structure validation
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