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Peptide-triggered conformational switch in HIV-1 RRE RNA complexes
Y Gosser1, T Hermann, A Majumdar
1Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Nature Structural Biology
|February 15, 2001
Summary
A high-affinity peptide binds HIV-1 RRE-IIB RNA in a unique conformation, altering a uridine base. This structural switch, visualized by NMR, highlights peptide sequence influence on RNA binding sites.
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- The Rev responsive element (RRE) of HIV-1 mRNA is crucial for viral gene expression.
- Understanding RNA-peptide interactions is key to developing antiviral therapies.
- Previous studies characterized Rev peptide binding to RRE-IIB.
Purpose of the Study:
- To determine the solution structure of the complex between HIV-1 RRE-IIB RNA and a high-affinity Arg-rich peptide.
- To compare this structure with that of a Rev peptide-RRE-IIB complex.
- To elucidate the role of peptide sequence in modulating the RNA binding site conformation.
Main Methods:
- Nuclear Magnetic Resonance (NMR) spectroscopy was employed to determine the complex's solution structure.
- NMR chemical shift mapping was used to visualize conformational changes.
- Competition experiments were conducted to assess binding affinities.
Main Results:
- The high-affinity peptide adopts a partially alpha-helical conformation.
- The peptide binds within a pocket in the deep groove of RRE-IIB.
- A conformational switch of an unpaired uridine base was observed, stabilized by Arg side chain stacking.
Conclusions:
- The bound peptide's sequence dictates the local conformation of the RRE peptide binding site.
- A specific Arg side chain interaction stabilizes a uridine base within the RNA deep groove.
- NMR chemical shift mapping effectively visualizes peptide-induced conformational changes in RNA.