Conformational Changes in HIV-1 Reverse Transcriptase that Facilitate Its Maturation
| Autor: | Nicolas Sluis Cremer, Ryan L. Slack, Rieko Ishima, Gota Kawai, Nicholas S. Giacobbi, Tatiana V Ilina, Michael A. Parniak, Stefan G. Sarafianos, Zhaoyong Xi |
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| Rok vydání: | 2019 |
| Předmět: |
Models
Molecular Protein Conformation Proteolysis medicine.medical_treatment Protein subunit Cleavage (embryo) Article 03 medical and health sciences Protein structure HIV Protease Structural Biology medicine Ribonuclease Molecular Biology Nuclear Magnetic Resonance Biomolecular 030304 developmental biology 0303 health sciences Protease medicine.diagnostic_test biology Chemistry 030302 biochemistry & molecular biology RNA Reverse transcriptase HIV Reverse Transcriptase Cell biology biology.protein HIV-1 RNA Transfer Lys Protein Multimerization |
| Zdroj: | Structure |
| ISSN: | 1878-4186 |
| Popis: | HIV-1 reverse transcriptase (RT) is translated as part of the Gag-Pol polyprotein that is proteolytically processed by HIV-1 protease (PR) to finally become a mature heterodimer, composed of a p66 and a p66-derived 51 kDa subunit, p51. Our prior work suggested that tRNA(Lys3) binding to p66/p66 introduces conformational changes in the ribonuclease (RNH) domain of RT that facilitate efficient cleavage of p66 to p51 by PR. In this study, we characterized the conformational changes in the RNH domain of p66/p66 imparted by tRNA(Lys3) using NMR. Moreover, the importance of tRNA(Lys3) in RT maturation was confirmed in cellulo by modulating the levels of Lys-tRNA synthetase, which affects recruitment of tRNA(Lys3) to the virus. We also employed nonnucleoside RT inhibitors, to modulate the p66 dimer–monomer equilibrium and monitor the resulting structural changes. Taken together, our data provide unique insights into the conformational changes in p66/p66 that drive PR cleavage. |
| Databáze: | OpenAIRE |
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