Abstract
RETROVIRUSES encode a protease which needs to be active for the production of infectious virions. A disabling mutation in the protease results in the production of non-infectious virus particles and examination of proteins from these mutant virions reveals unprocessed Gag and Gag-Pol precursor proteins, the substrates of the viral protease1-3. Each amino acid of the HIV-1 protease was individually mutated using a simple mutagenesis procedure which is capable of introducing and identifying missense mutations in each residue of a protein. Phenotypic screening of these mutants in a heterologous assay system reveals three regions within the protease where multiple consecutive amino-acid residues are sensitive to mutation. These results show that random mutagenesis can be used to identify functionally important regions within a protein. Mutants with conditional phenotypes have also been identified within this collection.
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Loeb, D., Swanstrom, R., Everitt, L. et al. Complete mutagenesis of the HIV-1 protease. Nature 340, 397–400 (1989). https://doi.org/10.1038/340397a0
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DOI: https://doi.org/10.1038/340397a0
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