CBP KIX 结构域的亮氨酸 628 是与 MLL 转录激活结构域相互作用的关键残基。
Leu628 of the KIX domain of CBP is a key residue for the interaction with the MLL transactivation domain.
机构信息
Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
出版信息
FEBS Lett. 2010 Nov 19;584(22):4500-4. doi: 10.1016/j.febslet.2010.10.024. Epub 2010 Oct 20.
Abstract
Physical interaction between the transactivation domain (TAD) of the mixed-lineage leukemia protein (MLL) and the KIX domain of the cyclic-AMP response element binding protein (CREB) binding protein (CBP) is necessary for MLL-mediated transcriptional activation. We show by alanine-scanning mutagenesis that hydrophobic surface residues of KIX, especially L628, are energetically important for binding the MLL TAD. NMR studies of the KIX-L628A mutant suggest that L628 plays a crucial role in conformational transitions at the MLL binding site, necessary for high affinity interactions with MLL. Unexpectedly, MLL also binds to the c-Myb/phosphorylated kinase-inducible domain of CREB (pKID) site of KIX, highlighting the complex nature of interactions involving intrinsically disordered transcriptional activators.
摘要
混合谱系白血病蛋白（MLL）的转录激活结构域（TAD）与环磷酸腺苷反应元件结合蛋白（CREB）结合蛋白（CBP）的 KIX 结构域之间的物理相互作用对于 MLL 介导的转录激活是必需的。我们通过丙氨酸扫描诱变表明，KIX 的疏水面残基，特别是 L628，对于结合 MLL TAD 具有重要的能量意义。对 KIX-L628A 突变体的 NMR 研究表明，L628 在 MLL 结合位点的构象转变中起着至关重要的作用，这对于与 MLL 高亲和力相互作用是必需的。出乎意料的是，MLL 还与 KIX 的 c-Myb/磷酸化激酶诱导结构域（pKID）位点结合，突出了涉及固有无序转录激活物的相互作用的复杂性质。
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