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The solution structure of HIV-1 Nef reveals an unexpected fold and permits delineation of the binding surface for the SH3 domain of Hck tyrosine protein kinase

Nature Structural Biology volume 3, pages 340–345 (1996)Cite this article

Abstract

The solution structure of HIV-1 Nef has been solved by multidimensional heteronuclear NMR spectroscopy. The construct employed to circumvent problems associated with aggregation was a double-deletion mutant (Δ2–39, Δ159–173) in which conformationally disordered regions of the protein at the N terminus and in a long solvent-exposed flexible loop were removed, without affecting the properties or structural integrity of the remainder of the protein. Despite the absence of any sequence similarity, the overall fold of Nef is reminiscent of that of the family of winged helix-turn-helix DNA binding proteins. The binding surface of Nef for the SH3 domain of Hck tyrosine protein kinase has been mapped and reveals a non-contiguous (in terms of amino-acid sequence) interaction surface. This unique feature may suggest possible avenues for drug design aimed at inhibiting the interaction between Nef and SH3 domains.

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Authors and Affiliations

  1. Laboratory of Chemical Physics, Building 5, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, 20892, USA

    Stephan Grzesiek, Ad Bax, G. Marius Clore, Angela M. Gronenborn & Jin-Shan Hu

  2. Protein Expression Laboratory, Building 6B, National Institute of Arthritis and Musculoskeletal Diseases, National Institutes of Health, Bethesda, Maryland, 20892, USA

    Joshua Kaufman, Ira Palmer, Stephen J. Stahl & Paul T Wingfield

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  1. Stephan Grzesiek
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  9. Paul T Wingfield
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Grzesiek, S., Bax, A., Clore, G. et al. The solution structure of HIV-1 Nef reveals an unexpected fold and permits delineation of the binding surface for the SH3 domain of Hck tyrosine protein kinase. Nat Struct Mol Biol 3, 340–345 (1996). https://doi.org/10.1038/nsb0496-340

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