title: Identification of amino acid residues in HIV-1 reverse transcriptase that are critical for the proteolytic processing of Gag-Pol precursors.
abstract: The efficient processing of human immunodeficiency virus type 1 Gag-Pol requires not only protease activity but also specific reverse transcriptase (RT) and integrase sequences. However, the critical amino acid residues of the HIV-1 Pol gene involved in protease-mediated Gag-Pol processing have not been precisely defined. Here, we found that the substitution of Thr-128 or Tyr-146 with Ala markedly impaired the proteolytic processing of the MA/CA, p66/p51 and RT/IN sites but did not affect the normal processing of other sites. Moreover, a Thr-128 or Tyr-146 mutation in RT abolished RT dimerization in vitro. These results suggest that Thr-128 and Tyr-146 within the RT region play important roles in protease-mediated Gag-Pol processing.
authors: Department of Life and Environmental Sciences, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan. hironori.nishitsuji@it-chiba.ac.jp
authors: Hironori
authors: H
authors: Nishitsuji
authors: Masaru
authors: M
authors: Yokoyama
authors: Hironori
authors: H
authors: Sato
authors: Suguru
authors: S
authors: Yamauchi
authors: Hiroshi
authors: H
authors: Takaku
mesh_terms: D019943:Amino Acid Substitution; D000596:Amino Acids; D015685:Fusion Proteins, gag-pol / Q000378:metabolism*; D057809:HEK293 Cells; D054303:HIV Reverse Transcriptase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D055503:Protein Multimerization; D011498:Protein Precursors / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D059748:Proteolysis; D014771:Virion / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014779:Virus Replication / Q000235:genetics
chemical_list: D000596:Amino Acids; D015685:Fusion Proteins, gag-pol; D011498:Protein Precursors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase