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TitleStructural insights into cationic amino acid transport and viral receptor engagement by CAT1.
Journal, issue, pagesNat Commun, Vol. 17, Issue 1, Page 1108, Year 2025
Publish dateDec 18, 2025
AuthorsLingyun Xia / Bingqian Lin / Rongfeng Zou / Yanyan Wu / Jiaying Xu / Yan Pan / Yuan Yuan / Shuo Li / Yang Yang / Xuemin Chen /
PubMed AbstractCationic amino acid transporter 1 (CAT1) transports cationic amino acids and plays pivotal roles in cancer proliferation, immune modulation, and nitric oxide metabolism. It also serves as the ...Cationic amino acid transporter 1 (CAT1) transports cationic amino acids and plays pivotal roles in cancer proliferation, immune modulation, and nitric oxide metabolism. It also serves as the specific cellular receptor for certain murine leukemia viruses. Here, we report the cryo-electron microscopy (cryo-EM) structure of mammalian CAT1 in complex with its substrate ornithine and the receptor-binding domain (RBD) of Friend murine leukemia virus (FrMLV). CAT1 specifically recognizes the side-chain amino group of ornithine via residue S347 on transmembrane helix 8 (TM8), capturing the transporter in an inward-facing occluded conformation. Notably, the FrMLV RBD (frRBD) primarily engages the third extracellular loop (ECL3) of CAT1-a region marked by substantial species-specific variation that likely governs cross-species viral tropism. Together, our structural and biochemical results elucidate the molecular mechanism of substrate recognition and transport by mCAT1, and unveil the molecular basis for FrMLV receptor specificity. These findings provide a valuable framework for structure-based drug design targeting CAT1 in cancer and infectious diseases.
External linksNat Commun / PubMed:41408058 / PubMed Central
MethodsEM (single particle)
Resolution3.65 Å
Structure data

EMDB-63995, PDB-9uat:
The structure of mCAT1 in complex with its substrate ornithine and the RBD of FrMLV.
Method: EM (single particle) / Resolution: 3.65 Å

Chemicals

ChemComp-ORN:
L-ornithine

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • mus musculus (house mouse)
  • friend murine leukemia virus (isolate 57)
KeywordsMEMBRANE PROTEIN / receptor / complex

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