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Research
Interest:
Human
immunodeficiency virus type 1 (HIV-1) viral assembly is mediated by
multiple
protein– protein and protein-nucleic acid interactions. Upon
infection, HIV-1
selectively packages the major human tRNALys
isoacceptors, tRNALys1,
2 and tRNALys3, where human tRNALys 3
acts as the primer for reverse transcription of
its RNA genome. Recruitment of this specific tRNA into newly forming
HIV-1
virions is thought to arise through its interaction with the tRNALys
binding protein, viz human
lysyl-tRNA synthetase (LysRS). This enzyme aminoacylates tRNALys
and gets incorporated into HIV-1. Thus this protein is a strong
candidate for
being the signal that specifically targets tRNALys
for viral
incorporation.
LysRS has
also
been shown to interact with Gag (1), one of the main structural
proteins in
HIV-1. Thus, this packaging complex serves as a potential target for
anti-HIV
therapy. My work is focused on studying the interaction between the
LysRS
protein and other ribonucleoprotein complexes such as tRNALys
and
Gag which are selectively packaged into the virus during its assembly.
Identification
of key residues involved in the interaction would potentially result in
elimination of tRNALys
in
newly packaged HIV-1 virions, resulting in the interruption of reverse
transcription.
Figure
1
HIV-1
life cycle (The
International Journal of Biochemistry
& Cell Biology. 36 (2004) 1776–1786).
References
- Javanbakht,
H., Halwani, R., Cen, S., Saadatmand, J., Musier-Forsyth, K.,
Gottlinger, H. & Kleiman, L. (2003).
The interaction between HIV-1 Gag and human lysyl-tRNA synthetase
during viral assembly. J. Biol. Chem. 278, 27644-27651.
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