Spronk C A, Tessari M, Kaan A M, Jansen J F, Vermeulen M, Stunnenberg H G, Vuister G W
Department of Biophysical Chemistry, NSR Center, University of Nijmegen, The Netherlands.
Nat Struct Biol. 2000 Dec;7(12):1100-4. doi: 10.1038/81944.
Sin3A or Sin3B are components of a corepressor complex that mediates repression by transcription factors such as the helix-loop-helix proteins Mad and Mxi. Members of the Mad/Mxi family of repressors play important roles in the transition between proliferation and differentiation by down-regulating the expression of genes that are activated by the proto-oncogene product Myc. Here, we report the solution structure of the second paired amphipathic helix (PAH) domain (PAH2) of Sin3B in complex with a peptide comprising the N-terminal region of Mad1. This complex exhibits a novel interaction fold for which we propose the name 'wedged helical bundle'. Four alpha-helices of PAH2 form a hydrophobic cleft that accommodates an amphipathic Mad1 alpha-helix. Our data further show that, upon binding Mad1, secondary structure elements of PAH2 are stabilized. The PAH2-Mad1 structure provides the basis for determining the principles of protein interaction and selectivity involving PAH domains.
Sin3A或Sin3B是一种共抑制复合物的组成成分，该复合物介导诸如螺旋-环-螺旋蛋白Mad和Mxi等转录因子的抑制作用。Mad/Mxi家族的抑制因子成员通过下调原癌基因产物Myc激活的基因表达，在增殖与分化的转变过程中发挥重要作用。在此，我们报道了Sin3B的第二个成对两亲螺旋（PAH）结构域（PAH2）与包含Mad1 N端区域的肽形成的复合物的溶液结构。该复合物展现出一种新型的相互作用折叠结构，我们将其命名为“楔形螺旋束”。PAH2的四个α螺旋形成一个疏水裂缝，可容纳一个两亲性的Mad1α螺旋。我们的数据进一步表明，与Mad1结合后，PAH2的二级结构元件得以稳定。PAH2-Mad1结构为确定涉及PAH结构域的蛋白质相互作用和选择性原则提供了基础。
