Ahmad K Farid, Melnick Ari, Lax Stuart, Bouchard Denis, Liu Jun, Kiang Chih-Li, Mayer Sebastian, Takahashi Shinichiro, Licht Jonathan D, Privé Gilbert G
Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2M9, Canada.
Mol Cell. 2003 Dec;12(6):1551-64. doi: 10.1016/s1097-2765(03)00454-4.
BCL6 encodes a transcription factor that represses genes necessary for the terminal differentiation of lymphocytes within germinal centers, and the misregulated expression of this factor is strongly implicated in several types of B cell lymphoma. The homodimeric BTB domain of BCL6 (also known as the POZ domain) is required for the repression activity of the protein and interacts directly with the SMRT and N-CoR corepressors that are found within large multiprotein histone deacetylase-containing complexes. We have identified a 17 residue fragment from SMRT that binds to the BCL6 BTB domain, and determined the crystal structure of the complex to 2.2 A. Two SMRT fragments bind symmetrically to the BCL6 BTB homodimer and, in combination with biochemical and in vivo data, the structure provides insight into the basis of transcriptional repression by this critical B cell lymphoma protein.
BCL6编码一种转录因子，该因子可抑制生发中心内淋巴细胞终末分化所必需的基因，并且该因子的表达失调与几种类型的B细胞淋巴瘤密切相关。BCL6的同二聚体BTB结构域（也称为POZ结构域）是该蛋白抑制活性所必需的，并且直接与在含大的多蛋白组蛋白去乙酰化酶的复合物中发现的SMRT和N-CoR共抑制因子相互作用。我们从SMRT中鉴定出一个与BCL6 BTB结构域结合的17个残基的片段，并确定了该复合物的晶体结构，分辨率为2.2埃。两个SMRT片段对称地结合到BCL6 BTB同二聚体上，结合生化和体内数据，该结构为这种关键的B细胞淋巴瘤蛋白的转录抑制基础提供了深入了解。
