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Peptide-triggered conformational switch in HIV-1 RRE RNA complexes

Nature Structural Biology volume 8, pages 146–150 (2001)Cite this article

Abstract

We have used NMR spectroscopy to determine the solution structure of a complex between an oligonucleotide derived from stem IIB of the Rev responsive element (RRE-IIB) of HIV-1 mRNA and an in vivo selected, high affinity binding Arg-rich peptide. The peptide binds in a partially α-helical conformation into a pocket within the RNA deep groove. Comparison with the structure of a complex between an α-helical Rev peptide and RRE-IIB reveals that the sequence of the bound peptide determines the local conformation of the RRE peptide binding site. A conformational switch of an unpaired uridine base was revealed; this points out into the solvent in the Rev peptide complex, but it is stabilized inside the RNA deep groove by stacking with an Arg side chain in the selected peptide complex. The conformational switch has been visualized by NMR chemical shift mapping of the uridine H5/H6 atoms during a competition experiment in which Rev peptide was displaced from RRE-IIB by the higher affinity binding selected peptide.

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Figure 1: The RSG-1.2–RRE-IIB complex.
Figure 2: The peptide binding sites in the RRE-IIB complexes.
Figure 3: Intermolecular contacts in the RSG-1.2–RRE-IIB complex.
Figure 4: Conformational transitions of U72.

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Acknowledgements

This research was supported by a NIH grant to D.J.P. X.Ye was involved in the early stages of this project and S. Park provided technical assistance in the preparation of the labeled peptide.

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Author notes

  1. Yuying Gosser and Thomas Hermann: Y.G. and T.H. contributed equally to this work.

Authors and Affiliations

  1. Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, 10021, New York, USA

    Yuying Gosser, Thomas Hermann, Ananya Majumdar, Weidong Hu, Ronnie Frederick, Feng Jiang, Weijun Xu & Dinshaw J. Patel

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  1. Yuying Gosser
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  2. Thomas Hermann
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Correspondence to Thomas Hermann or Dinshaw J. Patel.

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Gosser, Y., Hermann, T., Majumdar, A. et al. Peptide-triggered conformational switch in HIV-1 RRE RNA complexes. Nat Struct Mol Biol 8, 146–150 (2001). https://doi.org/10.1038/84138

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