The C domain in the surface envelope glycoprotein of subgroup C feline leukemia virus is a second receptor-binding domain.
The receptor-binding domain (RBD) in the surface (SU) subunit of gammaretrovirus envelope glycoprotein is critical for determining the host receptor specificity of the virus. This domain is separated from the carboxy terminal C domain (Cdom) of SU by a proline-rich region. In this study, we show that the Cdom region in the SU from subgroup C feline leukemia virus (FeLV-C) forms a second receptor-binding domain that is distinct from its RBD, and which can independently bind to its host receptor FLVCR1, in the absence of RBD. Furthermore, our results suggest that residues located in the C2 disulfide-bonded loop in FeLV-C Cdom are critical for SU binding to FLVCR1 and for virus infection. We propose that binding of FeLV-C SU to FLVCR1 involves interaction of two receptor-binding domains (RBD and Cdom) with FLVCR1, and that this mechanism of interaction is conserved for other gammaretroviruses. Our results could have important implications for designing gammaretrovirus vectors that can efficiently infect specific target cells.
Rey
Michelle A
MA
Program in Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada M5G 1X8.
Prasad
Rati
R
Tailor
Chetankumar S
CS
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002415:Cats; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D015686:Gene Products, env / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D006801:Humans; D005256:Leukemia Virus, Feline / Q000145:classification / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000235:genetics / Q000502:physiology; D015682:Retroviridae Proteins, Oncogenic / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D014774:Virulence
D017931:DNA Primers; D004279:DNA, Viral; C492690:FLVCR1 protein, human; D015686:Gene Products, env; D026901:Membrane Transport Proteins; D011991:Receptors, Virus; D015682:Retroviridae Proteins, Oncogenic; C051525:feline leukemia virus protein p15E