Substitution of a single amino acid residue is sufficient to allow the human amphotropic murine leukemia virus receptor to also function as a gibbon ape leukemia virus receptor.
We have previously reported the unique properties of a receptor for amphotropic murine leukemia viruses (A-MuLVs) expressed on Chinese hamster E36 cells (C.A. Wilson, K.B. Farrell, and M.V. Eiden, J. Virol. 68:7697-7703, 1994). This receptor, HaPiT2 (formerly designated EAR), in contrast to the human form of the A-MuLV receptor (PiT2), functions as a receptor not only for A-MuLVs but also for gibbon ape leukemia virus (GALV). Comparison of the deduced amino acid sequences of the HaPiT2 and PiT2 proteins suggested that differences in the amino acid composition of the extracellular region(s) of the hamster and human proteins account for their functional differences. We substituted extracellular regions of HaPiT2 for those of PiT2 to map the region of the HaPiT2 protein required for GALV receptor function. Only those PiT2-HaPiT2 chimeric receptors containing the fourth and fifth extracellular regions of HaPiT2 functioned as GALV receptors. We have now determined that the substitution of a single amino acid residue, glutamic acid, for the lysine residue at position 522 in the fourth extracellular region of the PiT2 protein is sufficient to render PiT2 functional as a GALV receptor.
Eiden
M V
MV
Laboratory of Cell Biology, National Institute of Mental Health, Bethesda, Maryland 20892, USA.
Farrell
K B
KB
Wilson
C A
CA
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D005256:Leukemia Virus, Feline / Q000472:pathogenicity; D017989:Leukemia Virus, Gibbon Ape / Q000378:metabolism*; D009052:Leukemia Virus, Murine / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008969:Molecular Sequence Data; D011991:Receptors, Virus / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
D011991:Receptors, Virus; D018698:Glutamic Acid; D008239:Lysine