Abstract

The investigator proposes to use the combined approaches of molecular genetics and NMR spectroscopy to probe the structural basis of protein/RNA interactions and to identify new means of preventing them. He proposes a more detailed analysis of the peptide backbone conformation of the RNA binding domain of HIV Tat to map the conformations of the amino-acyl side chains and to determine the structural basis for its strong and unexpected tendency for helix formation. The author then intends to prepare and characterize the complex formed by a short, biologically active Tat peptide with synthetic TAR RNA in order to assess the changes in RNA and protein conformation that occur upon binding and to identify potential targets for inhibitory drug design. The importance of any specific chemical contacts observed will be tested by mutating the nucleotides or amino acids involved and then examining the biologic and structural effects of the mutations.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI036636-01A1
Application #
2073035
Study Section
AIDS and Related Research Study Section 3 (ARRC)
Project Start
1994-12-01
Project End
1996-11-30
Budget Start
1994-12-01
Budget End
1995-11-30
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Pathology
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Mujeeb, Anwer; Ulyanov, Nikolai B; Georgantis, Stefanos et al. (2007) Nucleocapsid protein-mediated maturation of dimer initiation complex of full-length SL1 stemloop of HIV-1: sequence effects and mechanism of RNA refolding. Nucleic Acids Res 35:2026-34
Regan, John F; Liang, Yuying; Parslow, Tristram G (2006) Defective assembly of influenza A virus due to a mutation in the polymerase subunit PA. J Virol 80:252-61
Ulyanov, Nikolai B; Mujeeb, Anwer; Du, Zhihua et al. (2006) NMR structure of the full-length linear dimer of stem-loop-1 RNA in the HIV-1 dimer initiation site. J Biol Chem 281:16168-77
Ly, Hinh; Schertzer, Mike; Jastaniah, Wasil et al. (2005) Identification and functional characterization of 2 variant alleles of the telomerase RNA template gene (TERC) in a patient with dyskeratosis congenita. Blood 106:1246-52
Ly, Hinh; Calado, Rodrigo T; Allard, Paulette et al. (2005) Functional characterization of telomerase RNA variants found in patients with hematologic disorders. Blood 105:2332-9
Ly, Hinh; Xu, Lifeng; Rivera, Melissa A et al. (2003) A role for a novel 'trans-pseudoknot' RNA-RNA interaction in the functional dimerization of human telomerase. Genes Dev 17:1078-83
Ly, Hinh; Blackburn, Elizabeth H; Parslow, Tristram G (2003) Comprehensive structure-function analysis of the core domain of human telomerase RNA. Mol Cell Biol 23:6849-56
Clever, J L; Taplitz, R A; Lochrie, M A et al. (2000) A heterologous, high-affinity RNA ligand for human immunodeficiency virus Gag protein has RNA packaging activity. J Virol 74:541-6
Mujeeb, A; Parslow, T G; Zarrinpar, A et al. (1999) NMR structure of the mature dimer initiation complex of HIV-1 genomic RNA. FEBS Lett 458:387-92
Clever, J L; Eckstein, D A; Parslow, T G (1999) Genetic dissociation of the encapsidation and reverse transcription functions in the 5' R region of human immunodeficiency virus type 1. J Virol 73:101-9

Showing the most recent 10 out of 14 publications