mino acid and viral binding by the high-affinity Cationic Amino acid Transporter 1 (CAT1) from Mus musculus
Ye M., Liang Z., Zhou D., Pike ACW., Wang S., Wang D., Bakshi S., Brooke L., Williams EP., Elkins JM., Kessler BM., Stuart DI., Sauer DB.
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.