Grzesiek S, Bax A, Clore G M, Gronenborn A M, Hu J S, Kaufman J, Palmer I, Stahl S J, Wingfield P T
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nat Struct Biol. 1996 Apr;3(4):340-5. doi: 10.1038/nsb0496-340.
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 (delta2-39, delta159-173) 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.
HIV-1 Nef的溶液结构已通过多维异核核磁共振光谱法解析。为避免与聚集相关的问题而采用的构建体是一个双缺失突变体（δ2 - 39，δ159 - 173），其中蛋白质N端和一个长的溶剂暴露柔性环中构象无序的区域被去除，而不影响蛋白质其余部分的性质或结构完整性。尽管Nef与任何序列都没有相似性，但其整体折叠结构让人联想到有翼螺旋 - 转角 - 螺旋DNA结合蛋白家族。已绘制出Nef与Hck酪氨酸蛋白激酶SH3结构域的结合表面，揭示了一个非连续（就氨基酸序列而言）的相互作用表面。这一独特特征可能为旨在抑制Nef与SH3结构域之间相互作用的药物设计指明可能的途径。
