title: Molecular dynamics simulation and experimental verification of the interaction between cyclin T1 and HIV-1 Tat proteins.
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.
authors.affiliation: Department of Molecular and Cellular Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Asamitsu
authors.affiliation: Molecular Profiling Research Center for Drug Discovery (molprof), National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Tokyo, Japan.
authors.forename: Takatsugu
authors.initials: T
authors.lastname: Hirokawa
authors.affiliation: Department of Molecular and Cellular Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors.forename: Yurina
authors.initials: Y
authors.lastname: Hibi
authors.affiliation: Department of Molecular and Cellular Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Okamoto
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D056906:Cyclin T / Q000737:chemistry* / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000378:metabolism
chemical_list: D056906:Cyclin T; D054322:tat Gene Products, Human Immunodeficiency Virus