       Document 0318
 DOCN  M9610318
 TI    The structure of the human immunodeficiency virus type-1 TAR RNA reveals
       principles of RNA recognition by Tat protein.
 DT    9601
 AU    Aboul-ela F; Karn J; Varani G; MRC Laboratory of Molecular Biology,
       Cambridge, UK.
 SO    J Mol Biol. 1995 Oct 20;253(2):313-32. Unique Identifier : AIDSLINE
       MED/96036764
 AB    The human immunodeficiency virus type-1 (HIV-1) Tat protein stimulates
       transcriptional elongation. Tat is introduced to the transcription
       machinery by binding to the transactivation response region (TAR) RNA
       stem-loop encoded by the 5' leader sequence found on all HIV-1 mRNAs. We
       have used multidimensional heteronuclear NMR to determine the structure
       of the TAR RNA in the presence of the ADP-1 polypeptide, a 37-mer that
       carries the minimal RNA recognition region of the Tat protein and
       closely mimics Tat binding specificity. In the presence of a variety of
       ligands, including ADP-1, related basic peptides and the amino acid
       derivative argininamide, the bulge region of TAR undergoes a local
       conformational rearrangement and forms a more stable structure. The
       structure of TAR in the bound form has been determined from over 1000
       NMR-derived constraints. The U23 residue at the 5' end of the bulge is
       positioned near G26 and A27 in the major groove, rather than stacked on
       A22 as in the free TAR. U23 and G26 are brought into close proximity by
       contacts to the guanidinium group and side-chain amide group of a common
       arginine residue. However, the interaction of this guanidinium group
       with TAR is not the only source of binding specificity. Besides NOEs to
       the arginine residue participating in the conformational change, ADP-1
       shows additional intermolecular NOEs to TAR, suggesting that there are
       multiple points of contacts between TAR RNA and residues from the basic
       and core regions of Tat. These structural results provide important
       clues towards the identification of small molecular mass and/or
       peptidomimetic inhibitors of the essential Tat-TAR interaction.
 DE    Amino Acid Sequence  Bacterial
       Proteins/BIOSYNTHESIS/*CHEMISTRY/*METABOLISM  Base Sequence  Binding
       Sites  Comparative Study  Exons  Gene Products, tat/*METABOLISM  Human
       Hydrogen Bonding  HIV-1/*GENETICS/*METABOLISM  Ligands  Membrane
       Proteins/BIOSYNTHESIS/*CHEMISTRY/*METABOLISM  Models, Molecular
       Molecular Sequence Data  Nuclear Magnetic Resonance  *Nucleic Acid
       Conformation  Oligoribonucleotides  *Protein Conformation  RNA,
       Viral/*CHEMISTRY/*METABOLISM  Sequence Homology, Amino Acid  Support,
       Non-U.S. Gov't  Transcription, Genetic  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

