The Y271 and I274 Amino Acids in Reverse Transcriptase of Human Immunodeficiency Virus-1 Are Critical to Protein StabilityReport as inadecuate




The Y271 and I274 Amino Acids in Reverse Transcriptase of Human Immunodeficiency Virus-1 Are Critical to Protein Stability - Download this document for free, or read online. Document in PDF available to download.

Reverse transcriptase RT of human immunodeficiency virus HIV-1 plays a key role in initiating viral replication and is an important target for developing anti-HIV drugs. Our previous study showed that two mutations Y271A and I274A in the turn RT Gln269-Arg277 abrogated viral replication, but the replication capacity and RT activity was discordant. In this study, we further investigated why alanine substitutions at these two sites would affect viral replication. We found that both RT activity and RT protein were almost undetectable in viral particles of these two mutants, although the Pr160gag-pol mutants were properly expressed, transported and incorporated. Using protease inhibition assay, we demonstrated a correlation between the degradation of the RT mutants and the activity of viral protease. Our native gel analysis indicated that the mutations at 271 and 274 amino acids might cause conformational changes, leading to the formation of higher order oligomers instead of dimers, resulting in increased protein instability and susceptibility to viral protease. Thus, residues 271 and 274 are critical to RT stability and resistance to viral protease. The conservation of the two amino acid residues among different strains of HIV-1 lent further support to this conclusion. The knowledge gained here may prove useful in drug design.



Author: Hao-Jie Zhang , Yong-Xiang Wang , Hao Wu, Dong-Yan Jin, Yu-Mei Wen , Bo-Jian Zheng

Source: http://plos.srce.hr/



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