Structure of a BCOR corepressor peptide in complex with the BCL6 BTB domain dimer
Structure of a BCOR corepressor peptide in complex with the BCL6 BTB domain dimer
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DOI：
10.1016/j.molcel.2007.12.026
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发表时间：
2008-02-15
期刊：
影响因子：
16
通讯作者：
Prive, Gilbert G.
中科院分区：
文献类型：
--
作者：
Ghetu, Alexandru F.;Corcoran, Connie M.;Prive, Gilbert G.
已知转录辅阻遏物 BCOR、SMRT 和 NCoR 竞争性地结合 BCL6 BTB 结构域，尽管 BCOR 与其他两种辅阻遏物没有可检测到的序列相似性。我们从 BCOR 中鉴定出一个直接与 BCL6 BTB 结构域结合的 17 个残基基序，并以 2.6 埃的分辨率确定了复合物的晶体结构。值得注意的是，BCOR BCL6 结合结构域 (BCORBBD) 肽与 SMRTBD 肽结合在相同的 BCL6 结合位点，尽管这两种肽之间缺乏任何显着的序列相似性。关键 BCORBBD 残基的突变会导致 BCOR 的 BCL6 共抑制活性破坏，BCORBBD 肽可阻断 BCL6 介导的转录抑制并杀死淋巴瘤细胞。
The transcriptional corepressors BCOR, SMRT, and NCoR are known to bind competitively to the BCL6 BTB domain despite the fact that BCOR has no detectable sequence similarity to the other two corepressors. We have identified a 17 residue motif from BCOR that binds directly to the BCL6 BTB domain and determined the crystal structure of the complex to a resolution of 2.6 angstrom. Remarkably, the BCOR BCL6 binding domain (BCORBBD) peptide binds in the same BCL6 binding site as the SMRTBBD peptide despite the lack of any significant sequence similarity between the two peptides. Mutations of critical BCORBBD residues cause the disruption of the BCL6 corepression activities of BCOR, and a BCORBBD peptide blocks BCL6-mediated transcriptional repression and kills lymphoma cells.