Molecular dynamics simulation and experimental verification of the interaction between cyclin T1 and HIV-1 Tat proteins

PloS One
Kaori AsamitsuTakashi Okamoto

Abstract

The viral encoded Tat protein is essential for the transcriptional activation of HIV proviral DNA. Interaction of Tat with a cellular transcription elongation factor P-TEFb containing CycT1 is critically required for its action. In this study, we performed MD simulation using the 3D data for wild-type and 4CycT1mutants3D data. We found that the dynamic structural change of CycT1 H2' helix is indispensable for its activity for the Tat action. Moreover, we detected flexible structural changes of the Tat-recognition cavity in the WT CycT1 comprising of ten AAs that are in contact with Tat. These structural fluctuations in WT were lost in the CycT1 mutants. We also found the critical importance of the hydrogen bond network involving H1, H1' and H2 helices of CycT1. Since similar AA substitutions of the Tat-CycT1 chimera retained the Tat-supporting activity, these interactions are considered primarily involved in interaction with Tat. These findings described in this paper should provide vital information for the development of effective anti-Tat compound.

References

Aug 20, 1992·Journal of Molecular Biology·D F StickleG D Rose
Jun 1, 1994·Nature Structural Biology·V Muñoz, L Serrano
Dec 1, 1993·Proteins·A AmadeiH J Berendsen
Oct 25, 1996·The Journal of Biological Chemistry·N F MarshallD H Price
Apr 16, 1998·Genes & Development·J PengD H Price
Feb 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·K FujinagaB M Peterlin
Apr 27, 1992·Physical Review Letters·A E García
Jun 29, 1999·Cold Spring Harbor Symposia on Quantitative Biology·M E GarberK A Jones
Nov 5, 1999·Protein Science : a Publication of the Protein Society·M PetukhovL Serrano
Nov 5, 1999·Journal of Molecular Biology·J Karn
Jul 25, 2000·The Journal of Biological Chemistry·S H ChaoD H Price
Feb 28, 2002·Biochemical and Biophysical Research Communications·Lilen C SarolTakashi Okamoto
Mar 23, 2002·Protein Science : a Publication of the Protein Society·Michael PetukhovLuis Serrano
Mar 5, 2004·The New England Journal of Medicine·François Clavel, Allan J Hance
Apr 23, 2004·Current Opinion in Structural Biology·Chern-Sing GohMark Gerstein
Aug 4, 2006·Molecular Cell·B Matija Peterlin, David H Price
Jun 11, 2010·Nature·Tahir H TahirovDavid H Price
Apr 15, 2014·Cell Cycle·Jianyou GuTahir H Tahirov
May 9, 2014·Cell Biochemistry and Biophysics·V Karthick, K Ramanathan

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Citations

May 20, 2016·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Kaori AsamitsuTakashi Okamoto
Aug 4, 2018·Cell Biochemistry and Biophysics·Kgothatso E MachabaMahmoud E S Soliman
Nov 16, 2018·Journal of Medical Virology·Muhammad Usman MirzaMuhammad Idrees
Apr 21, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kaori AsamitsuTakashi Okamoto

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Methods Mentioned

BETA
NMR
PCA
PCR
Assay
transfection
immunoprecipitation
co-immunoprecipitation

Software Mentioned

AMBER
LeaP
Molecular Operating Environment ( MOE )
PyMol
ContactAnalyzer
MOE ContactAnalyzer
R
ptraj
AMBER11
molprof

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