title: Structure-based analysis of the molecular recognitions between HIV-1 TAR-RNA and transcription factor nuclear factor-kappaB (NFkB).
abstract: In this paper we applied the "macromolecular docking" procedure to perform molecular modeling with the aim of screening transcription factor sequences for possible interaction to the HIV-1 TAR-RNA, employing the software Hex version 4.2. The molecular modeling data were compared with electrophoretic mobility shift assays (EMSA) and surface plasmon resonance (SPR) based biospecific interaction analysis (BIA) using an optical biosensor. Finally the specific interactions between NF-κB and RNA have been calculated utilizing the AMBER-MM and FMO calculations. The results obtained clearly indicate that (a) NF-kB p50 transcription factor can bind TAR-RNA; (b) this binding efficiency is lower than that displayed by NF-kB factor in respect to DNA sequences; (c) other structured RNAs used as controls do not bind to NF-kB; (d) TAR-RNA is capable to bind pre-formed NF-kB/DNA complexes. Despite the fact that our data do not indicate whether NF-kB/TAR-RNA complexes play a role in the early steps of HIV-1 transcriptional activation, the results presented strongly indicate that interactions between transcription factors recruited at the level of HIV-1 LTR might interact with the TAR-RNA and deserve further studies aimed to determine its role in the HIV-1 life cycle.
authors.affiliation: Department of Biochemistry and Molecular Biology, Section of Molecular Biology, University of Ferrara, Via Fossato di Mortara 74, Ferrara I-44100, Italy. mthkhan@uic.edu
authors.forename: Mahmud Tareq Hassan
authors.initials: MT
authors.lastname: Khan
authors.forename: Carlo
authors.initials: C
authors.lastname: Mischiati
authors.forename: Arjumand
authors.initials: A
authors.lastname: Ather
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ohyama
authors.forename: Kenichi
authors.initials: K
authors.lastname: Dedachi
authors.forename: Monica
authors.initials: M
authors.lastname: Borgatti
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kurita
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
mesh_terms: D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D016328:NF-kappa B / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics
chemical_list: D016328:NF-kappa B; D012367:RNA, Viral