Interaction of HIV Tat model peptides with tRNA and 5S rRNA.

New data are presented on the interaction of model synthetic peptides containing an arginine-rich region of human immunodeficiency virus (HIV-Tat), with native RNA molecules: tRNA(Phe) of Saccharomyces cerevisiae and 5S rRNA from Lupinus luteus. Both RNA species form complexes with the Tat1 (GRKKRRQRRRA) and Tat2 (GRKKRRQRRRAPQDSQTHQASLSKQPA) peptides, as shown by electrophoretic gel shift and RNase footprint assays, and CD measurements. The nucleotide sequence UGGG located in the dihydrouridine loop of tRNAPhe as well as in the loop D of 5S rRNA is specifically protected against RNases. Our data indicate direct interactions of guanine of RNA moieties with arginine residues. These interactions seem similar to those observed in DNA-protein complexes, but different from those previously observed in the TAR RNA-Tat complexes.

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Interaction of HIV Tat Peptides With tRNAPhe from Yeast

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19980842 ◽

1998 ◽

Vol 63 (6) ◽

pp. 842-850 ◽

Cited By ~ 2

Author(s):

Iwona Buskiewicz ◽

Malgorzata Giel-Pietraszuk ◽

Piotr Mucha ◽

Piotr Rekowski ◽

Gotfryd Kupryszewski ◽

...

Keyword(s):

Protein Complexes ◽

Tat Peptide ◽

Phosphodiester Bond ◽

Tat Peptides ◽

Hiv Tat ◽

Immunodeficiency Virus ◽

Arginine Residues ◽

Tar Rna ◽

Rna Complex ◽

Direct Recognition

We present data on the interaction of arginine-rich peptides of human immunodeficiency virus (HIV-Tat) with tRNAPhe of Saccharomyces cerevisiae. We have found that tRNA forms complexes with the Tat1 peptide of amino acid sequence GRKKRRQRRRA and its mutants where R is replaced by D-arginine, citrulline or ornithine. The structure of tRNA-Tat1 complex was probed by specific RNases digestions and Pb2+-induced cleavage of phosphodiester bond of guanosine. The nucleotide sequence UGGG located in the dihydrouridine loop of tRNAPhe binds to Tat peptide and therefore is specifically protected against RNases and is not hydrolyzed by Pb2+ ion. It seems that the peptide-RNA complex formation depends on direct recognition of guanine moieties of tRNA with arginine residues. These interactions are similar to those observed in many DNA-protein complexes, but are different from those previously observed for TAR RNA-Tat complexes.

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Membrane interactions of synthetic peptides corresponding to amphipathic helical segments of the human immunodeficiency virus type-1 envelope glycoprotein.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)50546-4 ◽

1992 ◽

Vol 267 (10) ◽

pp. 7121-7127

Author(s):

S.K. Srinivas ◽

R.V. Srinivas ◽

G.M. Anantharamaiah ◽

J.P. Segrest ◽

R.W. Compans

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Envelope Glycoprotein ◽

Synthetic Peptides ◽

Membrane Interactions ◽

Immunodeficiency Virus

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RNA AND N3′ → P5′ KISSING APTAMERS TARGETED TO THETRANS-ACTIVATION RESPONSIVE (TAR) RNA OF THE HUMAN IMMUNODEFICIENCY VIRUS-1

Nucleosides Nucleotides & Nucleic Acids ◽

10.1081/ncn-100002318 ◽

2001 ◽

Vol 20 (4-7) ◽

pp. 441-449 ◽

Cited By ~ 12

Author(s):

Fabien Darfeuille ◽

Christian Cazenave ◽

Sergei Gryaznov ◽

Frédéric Ducongé ◽

Carmelo Di Primo ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Immunodeficiency Virus ◽

Tar Rna ◽

Human Immunodeficiency Virus 1

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Monocytes Treated with Human Immunodeficiency Virus Tat Kill Uninfected CD4+ Cells by a Tumor Necrosis Factor-Related Apoptosis-Induced Ligand-Mediated Mechanism

Journal of Virology ◽

10.1128/jvi.77.12.6700-6708.2003 ◽

2003 ◽

Vol 77 (12) ◽

pp. 6700-6708 ◽

Cited By ~ 61

Author(s):

Yida Yang ◽

Ilia Tikhonov ◽

Tracy J. Ruckwardt ◽

Mahmoud Djavani ◽

Juan Carlos Zapata ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cells ◽

Cell Death ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Cell Surface Expression ◽

Monocyte Subset ◽

Hiv Tat ◽

Immunodeficiency Virus ◽

Necrosis Factor

ABSTRACT The human immunodeficiency virus (HIV) Tat protein has a critical role in viral transcription, but this study focuses on its additional role as an extracellular effector of lymphocyte cell death. It is well known that Tat induces tumor necrosis factor-related apoptosis-induced ligand (TRAIL) in peripheral blood mononuclear cells (PBMC), and we show that the majority of TRAIL is produced by the monocyte subset of PBMC. Human monocytes and U937 monoblastoid cells did not take up soluble HIV Tat-86, as T cells did, yet produced more TRAIL than did T cells. TRAIL secretion was induced by Tat and by a cysteine-rich peptide of Tat but not by sulfhydryl-modified Tat toxoid. Although there was only a slight increase in cell surface expression of TRAIL on monocytes, sufficient TRAIL was secreted to be toxic for T cells. The cytotoxicity of Tat-stimulated monocyte medium could be blocked by a TRAIL-neutralizing antibody. T cells treated with Tat did not secrete enough TRAIL to mediate cell death in our assay. Remarkably, uninfected T cells are more susceptible to TRAIL than are HIV-infected T cells. The production of TRAIL by Tat-stimulated monocytes provides a mechanism by which HIV infection can destroy uninfected bystander cells.

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A Proline-Rich Region in the Zeste Protein Essential for Transvection and white Repression by Zeste1

Genetics ◽

10.1093/genetics/148.4.1865 ◽

1998 ◽

Vol 148 (4) ◽

pp. 1865-1874

Author(s):

Christina Rosen ◽

Dale Dorsett ◽

Joseph Jack

Keyword(s):

Dna Binding ◽

Protein Interactions ◽

Homologous Chromosome ◽

Protein Complexes ◽

Dna Binding Protein ◽

Polycomb Group ◽

The Self ◽

Rich Region ◽

Interaction Domain ◽

Proline Rich Region

Abstract The DNA-binding protein encoded by the zeste gene of Drosophila activates transcription and mediates interchromosomal interactions such as transvection. The mutant protein encoded by the zeste1 (z1) allele retains the ability to support transvection, but represses white. Similar to transvection, repression requires Zeste-Zeste protein interactions and a second copy of white, either on the homologous chromosome or adjacent on the same chromosome. We characterized two pseudorevertants of z1 (z1-35 and z1-42) and another zeste mutation (z78c) that represses white. The z1 lesion alters a lysine residue located between the N-terminal DNA-binding domain and the C-terminal hydrophobic repeats involved in Zeste self-interactions. The z78c mutation alters a histidine near the site of the z1 lesion. Both z1 pseudorevertants retain the z1 lesion and alter different prolines in a proline-rich region located between the z1 lesion and the self-interaction domain. The pseudorevertants retain the ability to self-interact, but fail to repress white or support transvection at Ultrabithorax. To account for these observations and evidence indicating that Zeste affects gene expression through Polycomb group (Pc-G) protein complexes that epigenetically maintain chromatin states, we suggest that the regions affected by the z1, z78c, and pseudorevertant lesions mediate interactions between Zeste and the maintenance complexes.

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Synthetic peptides and anti-peptide antibodies as probes to study interdomain interactions involved in virus assembly: The envelope of the human immunodeficiency virus (HIV-1)

Virology ◽

10.1016/0042-6822(92)90729-9 ◽

1992 ◽

Vol 188 (1) ◽

pp. 1-13 ◽

Cited By ~ 30

Author(s):

A.R. Neurath ◽

N. Strick ◽

S. Jiang

Keyword(s):

Human Immunodeficiency Virus ◽

Synthetic Peptides ◽

Virus Assembly ◽

Immunodeficiency Virus ◽

Interdomain Interactions ◽

Hiv 1 ◽

Peptide Antibodies

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A functional genetic approach suggests a novel interaction between the human immunodeficiency virus type 1 (HIV-1) Tat protein and HIV-1 TAR RNA in vivo

Journal of General Virology ◽

10.1099/vir.0.18645-0 ◽

2003 ◽

Vol 84 (3) ◽

pp. 603-606 ◽

Cited By ~ 5

Author(s):

Lars H. Lund ◽

Britta Wahren ◽

Mariano A. Garcia-Blanco

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Tat Protein ◽

Cyclin T1 ◽

Immunodeficiency Virus ◽

Tar Rna ◽

Hiv 1

Human immunodeficiency virus type 1 (HIV-1) Tat and human Cyclin T1 form a complex and together recognize the viral TAR RNA element with specificity. Using HIV-1/equine infectious anaemia virus TAR chimeras, we show that in addition to the well-characterized interaction with the bulge, Tat recognizes the distal stem and the loop of TAR. These data support previously proposed, but unproven, molecular models.

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Exploring RNA-ligand interactions

Pure and Applied Chemistry ◽

10.1351/pac-con-08-08-16 ◽

2009 ◽

Vol 81 (2) ◽

pp. 263-272 ◽

Cited By ~ 18

Author(s):

Yitzhak Tor

Keyword(s):

Therapeutic Potential ◽

Protein Complexes ◽

Nucleoside Analogs ◽

Structural Similarity ◽

Absorption Bands ◽

Rna Molecules ◽

Design And Synthesis ◽

Cell Functions ◽

High Structural Similarity ◽

Ligand Interactions

RNA molecules play essential roles in biological processes and are evolving as important targets for therapeutic intervention. Small molecules that specifically bind unique RNA sites and prevent the formation of functional RNA folds or RNA-protein complexes can modulate cell functions and can become of therapeutic potential. To explore such recognition events and to fabricate discovery assays, effective biophysical tools need to be advanced. When carefully designed, new fluorescent nucleosides can serve an unparalleled role in such studies. Our criteria for "ideal" fluorescent nucleoside analogs include: (a) high structural similarity to the native nucleobases to faithfully mimic their size and shape, as well as hybridization and recognition properties; (b) red-shifted absorption bands; (c) red-shifted emission band (preferably in the visible); (d) a reasonable emission quantum efficiency; and, importantly, (e) sensitivity of their photophysical parameters to changes in the microenvironment. Our program, aimed at the development of new emissive isomorphic nucleoside analogs, has yielded several useful nucleobases. Selected analogs were implemented in fluorescence-based assays. This overview presents the motivation for this work by introducing RNA-ligand interactions and discusses the design and synthesis of fluorescent isosteric nucleobase analogs and their utilization for the fabrication of "real-time" fluorescence-based biophysical assays.

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