Molecular basis of the altered gag p19 protein (MA) of the transformation-defective mutant of Rous sarcoma virus, tdPH2010.

The transformation-defective mutant of Rous sarcoma virus (RSV), tdPH2010, has a gag p19 (matrix; MA) protein which migrates on SDS-polyacrylamide gels faster than that of the parental (tsNY68) as well as other wild-type strains of RSV. To study the molecular basis of this altered migration pattern and its biological significance, the nucleotide sequence of the p19 region of tdPH2010 was determined. Comparison of the nucleotide sequence of tdPH2010 with that of the Schmidt-Ruppin A strain of RSV revealed a point mutation at nucleotide 755 (G to A), resulting in an amino-acid substitution at residue 126 of p19 (Glu to Lys). Acidic-methanol esterification of free carboxyl groups suppressed the difference in electrophoretic mobility of p19 between tdPH2010 and the wild-type virus. Recombinant virus constructs having the mutated gag region of tdPH2010 produced a p19 with the same electrophoretic mobility as the p19 of tdPH2010. We concluded that the point mutation caused the altered electrophoretic behavior of p19 of tdPH2010. The mutation had no effect on the growth of infected cells.