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TitleAmino acid and viral binding by the high-affinity Cationic Amino acid Transporter 1 (CAT1) from Mus musculus.
Journal, issue, pagesNat Commun, Year 2026
Publish dateFeb 16, 2026
AuthorsMingda Ye / Zhu Liang / Daming Zhou / Ashley C W Pike / SiYi Wang / Dong Wang / Souvika Bakshi / Laurent Brooke / Eleanor P Williams / Jonathan M Elkins / Benedikt M Kessler / David I Stuart / David B Sauer /
PubMed AbstractArginine, lysine, and ornithine are critical to several fundamental aspects of organismal physiology, including protein structure and function, the urea cycle, and intracellular signaling. These ...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.
External linksNat Commun / PubMed:41698924
MethodsEM (single particle)
Resolution2.79 - 3.5 Å
Structure data

50668

9fqt

EMDB-50668, PDB-9fqt:
Cryo-EM structure of MmCAT1 bound with FrMLV-RBD in the apo inward-open state
Method: EM (single particle) / Resolution: 3.5 Å

50669

9fqu

EMDB-50669, PDB-9fqu:
Cryo-EM structure of MmCAT1 bound with FrMLV-RBD in the arginine-bound inward-occluded state
Method: EM (single particle) / Resolution: 2.79 Å

50670

9fqv

EMDB-50670, PDB-9fqv:
Cryo-EM structure of MmCAT1 bound with FrMLV-RBD in the lysine-bound inward-occluded state
Method: EM (single particle) / Resolution: 2.95 Å

50671

9fqw

EMDB-50671, PDB-9fqw:
Cryo-EM structure of MmCAT1 bound with FrMLV-RBD in the ornithine-bound inward-occluded state
Method: EM (single particle) / Resolution: 3.01 Å

Chemicals

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

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

ChemComp-ARG:
ARGININE

ChemComp-HOH:
WATER

ChemComp-LYS:
LYSINE

ChemComp-ORN:
L-ornithine

Source
  • mus musculus (house mouse)
  • murine leukemia virus
KeywordsMEMBRANE PROTEIN / MmCAT1 / FrMLV-RBD / SLC / viral tropism

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