Structure and mechanism of a coreceptor for infection by a pathogenic feline retrovirus.
Infection of T lymphocytes by the cytopathic retrovirus feline leukemia virus subgroup T (FeLV-T) requires FeLIX, a cellular coreceptor that is encoded by an endogenous provirus and closely resembles the receptor-binding domain (RBD) of feline leukemia virus subgroup B (FeLV-B). We determined the structure of FeLV-B RBD, which has FeLIX activity, to a 2.5-A resolution by X-ray crystallography. The structure of the receptor-specific subdomain of this glycoprotein differs dramatically from that of Friend murine leukemia virus (Fr-MLV), which binds a different cell surface receptor. Remarkably, we find that Fr-MLV RBD also activates FeLV-T infection of cells expressing the Fr-MLV receptor and that FeLV-B RBD is a competitive inhibitor of infection under these conditions. These studies suggest that FeLV-T infection relies on the following property of mammalian leukemia virus RBDs: the ability to couple interaction with one of a variety of receptors to the activation of a conserved membrane fusion mechanism. A comparison of the FeLV-B and Fr-MLV RBD structures illustrates how receptor-specific regions are linked to conserved elements critical for postbinding events in virus entry.
Barnett
Anna L
AL
Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Wensel
David L
DL
Li
Weihua
W
Fass
Deborah
D
Cunningham
James M
JM
D000595:Amino Acid Sequence; D000818:Animals; D002415:Cats; D002460:Cell Line; D006224:Cricetinae; D003460:Crystallization; D018360:Crystallography, X-Ray; D006023:Glycoproteins / Q000737:chemistry; D006801:Humans; D005256:Leukemia Virus, Feline / Q000378:metabolism / Q000472:pathogenicity*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011991:Receptors, Virus / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment; D014759:Viral Envelope Proteins / Q000737:chemistry
C108061:Fr-RBD protein, Friend murine leukemia virus; D006023:Glycoproteins; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; C074548:feline leukemia virus receptor