Amino acid and viral binding by the high-affinity Cationic Amino acid Transporter 1 (CAT1) from Mus musculus
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Abstract
Arginine, lysine, and ornithine are critical to several fundamental aspects of organismal physiology, including protein structure and function, the urea cycle, and intracellular signaling. These cationic amino acids are imported by several membrane transporters, most notably the Cationic Amino acid Transporters (CATs) in the SLC7 family. Of these, CAT1 is also the receptor for two orthoretroviruses, and determines the host tropism for these viruses. Here, using a combination of CryoEM and in vitro biochemical techniques, we characterize the substrate recognition and transport of CAT1 from Mus musculus . Further, by determining the structures of MmCAT1 in complex with the receptor binding domain from the Friend Murine Leukemia Virus, we identify the key structural interactions that determine the virus’ rodent-specific tropism.
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- Authors
- Ye, M., Liang, Z., Zhou, D., Pike, A. C. W., Wang, S., Wang, D., Bakshi, S., Brooke, L., Williams, E. P., Elkins, J. M., Kessler, B. M., Stuart, D. I., & Sauer, D. B.
- Affiliations
- University of Oxford (GB)
- Centre for Human Genetics (GB)
- Corresponding author
- Sauer, David B.
- ORCID
- Venue
- Nature Communications
- Published
- 2026-02-16
- Volume
- 17
- Issue
- 1
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W7129003891
- Cited by
- 1
- References
- 65
- Citations by year
- 2026: 1
- FWCI
- 2.30
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Innovative Medicines Initiative (875510, 807015)
- Chinese Academy of Medical Sciences (2024-I2M-2-001-1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- CAT1, cationic amino acid transport, L-arginine, lysine, ornithine, substrate recognition, viral receptor binding, Friend murine leukemia virus, host tropism, transporter structure, Mus musculus
- MeSH terms
- Amino Acids, Animals, Leukemia Virus, Murine, Protein Binding, Cryoelectron Microscopy, Cationic Amino Acid Transporter 1, Mice
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