Complete mutagenesis of the HIV-1 protease

Nature. 1989 Aug 3;340(6232):397-400. doi: 10.1038/340397a0.


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 protease. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Blotting, Western
  • Cloning, Molecular
  • Endopeptidases / genetics*
  • Endopeptidases / metabolism
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Gene Products, gag
  • HIV Protease
  • HIV-1 / enzymology*
  • HIV-1 / genetics
  • Molecular Sequence Data
  • Mutation*
  • Phenotype
  • Protein Precursors / metabolism
  • Retroviridae Proteins / metabolism
  • Transformation, Bacterial


  • Gene Products, gag
  • Protein Precursors
  • Retroviridae Proteins
  • Endopeptidases
  • HIV Protease