Abstract

As a model for understanding RNA-protein interactions we are studying the structure of the Rev-Response Element RNA in complex with peptides derived from thRev protein. Rev is one of two small basic regulatory protein in HIV. Binding of Rev to the Rev-response element RNA (RRE) results in a change in the ratio of spliced and unspliced viral mRNAs that appear in the cytoplasm. Formation of this interaction is a key point in the replication cycle of HIV. The structure determination of this RNA-peptide complex is nearly complete. Nine different samples have been prepared with various isotopic labeling combinations in the RNA and peptides. Approximately 100 torsion restraints, 400 RNA NOE restraints, 350 peptide NOE restraints, and 60 RNA-peptide NOE restraints have been collected. Preliminary structure calculations reveal that an alpha-helical peptide is inserted into the major groove of the RNA, which adopts an unusual structure due to the presence to two purine-purine base pairs.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR000995-21
Application #
5221895
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
21
Fiscal Year
1996
Total Cost
Indirect Cost

  Publications

Marintchev, Assen; Edmonds, Katherine A; Marintcheva, Boriana et al. (2009) Topology and regulation of the human eIF4A/4G/4H helicase complex in translation initiation. Cell 136:447-60
Frueh, Dominique P; Arthanari, Haribabu; Koglin, Alexander et al. (2009) A double TROSY hNCAnH experiment for efficient assignment of large and challenging proteins. J Am Chem Soc 131:12880-1
Frueh, Dominique P; Leed, Alison; Arthanari, Haribabu et al. (2009) Time-shared HSQC-NOESY for accurate distance constraints measured at high-field in (15)N-(13)C-ILV methyl labeled proteins. J Biomol NMR 45:311-8
Lentz, Margaret R; Westmoreland, Susan V; Lee, Vallent et al. (2008) Metabolic markers of neuronal injury correlate with SIV CNS disease severity and inoculum in the macaque model of neuroAIDS. Magn Reson Med 59:475-84
Chen, Jingyang; Dupradeau, Francois-Yves; Case, David A et al. (2007) Nuclear magnetic resonance structural studies and molecular modeling of duplex DNA containing normal and 4'-oxidized abasic sites. Biochemistry 46:3096-107
Hyberts, Sven G; Heffron, Gregory J; Tarragona, Nestor G et al. (2007) Ultrahigh-resolution (1)H-(13)C HSQC spectra of metabolite mixtures using nonlinear sampling and forward maximum entropy reconstruction. J Am Chem Soc 129:5108-16
Lentz, Margaret R; Kim, John P; Westmoreland, Susan V et al. (2005) Quantitative neuropathologic correlates of changes in ratio of N-acetylaspartate to creatine in macaque brain. Radiology 235:461-8
Kim, John P; Lentz, Margaret R; Westmoreland, Susan V et al. (2005) Relationships between astrogliosis and 1H MR spectroscopic measures of brain choline/creatine and myo-inositol/creatine in a primate model. AJNR Am J Neuroradiol 26:752-9
Peled, S; Cory, D G; Raymond, S A et al. (1999) Water diffusion, T(2), and compartmentation in frog sciatic nerve. Magn Reson Med 42:911-8
Mo, H; Dai, Y; Pochapsky, S S et al. (1999) 1H, 13C and 15N NMR assignments for a carbon monoxide generating metalloenzyme from Klebsiella pneumoniae. J Biomol NMR 14:287-8

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