Aj. Mackrell et al., IDENTIFICATION OF A SUBDOMAIN IN THE MOLONEY MURINE LEUKEMIA-VIRUS ENVELOPE PROTEIN INVOLVED IN RECEPTOR-BINDING, Journal of virology, 70(3), 1996, pp. 1768-1774
We have mutated amino acids within the receptor-binding domain of Molo
ney murine leukemia virus envelope in order to identify residues invol
ved in receptor binding, Analysis of mutations in the region of amino
acids 81 to 88 indicates that this region is important for specific en
velope-receptor interactions, None of the aspartate 84 (D-84) mutants
studied bind measurably, although they are efficiently incorporated in
to particles, D-84 mutants have titers that correspond to the severity
of the substitution, This observation suggests that D-84 may provide
a direct receptor contact, Mutations in the other charged amino acids
in this domain (R-83, E-86, and E-87) yield titers similar to those of
wild-type envelope, but the affinity of the mutant envelope in the bi
nding assay is decreased by nonconservative substitutions in parallel
to the severity of the change, These other amino acids may either prov
ide secondary receptor contacts or assist in maintaining a structure i
n the domain that favors efficient binding, We also studied other regi
ons of high hydrophilicity. Our initial characterization indicates tha
t amino acids 106 to 111 and 170 to 188 do not play a major role in re
ceptor binding, Measurements of relative binding affinity and titer in
dicate that most mutations in the region of amino acids 120 to 131 did
not significantly affect receptor binding, However, SU encoded by mut
ants H123V, R124L, and C131A as well as C81A could not be detected in
particles and therefore did not bind measurably, Therefore, the region
encompassed by amino acids 81 to 88 appears to be directly involved i
n receptor binding.