Crystal structure of the BTB domain from the LRF/ZBTB7 transcriptional regulator
Crystal structure of the BTB domain from the LRF/ZBTB7 transcriptional regulator
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DOI：
10.1110/ps.062660907
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发表时间：
2007-02-01
期刊：
影响因子：
8
通讯作者：
Prive, Gilbert G.
中科院分区：
文献类型：
--
作者：
Stogios, Peter J.;Chen, Lu;Prive, Gilbert G.
BTB-锌指 (BTB-ZF) 蛋白是转录调节因子，在发育、分化和肿瘤发生中发挥作用。在这些蛋白质中，BTB 结构域（也称为 POZ 结构域）是蛋白质-蛋白质相互作用基序，包含二聚化界面、可能的寡聚化表面以及与其他因子（包括核共阻遏物和组蛋白脱乙酰酶）相互作用的表面。 BTB-ZF 蛋白 LRF（也称为 ZBTB7、FBI-1、OCZF 和 Pokemon）是肿瘤发生的主要调节因子，抑制多种重要基因的转录，包括 ARF、c-fos 和 c-myc 癌基因和细胞外基质基因。我们确定了从人类 LRF 到 2.1 埃的 BTB 结构域的晶体结构，并观察到了典型的 BTB 同二聚体折叠。然而，同型二聚体的表面上有明显的新特征，包括侧向凹槽和带电口袋区域的差异。侧沟排列的残基与 BCL6 BTB 结构域中的等效残基几乎没有相似性，并且我们表明来自 SMRT 共阻遏物的 17 个残基 BCL6 结合结构域 (BBD) 不与 LRF BTB 结构域结合。
BTB-zinc finger (BTB-ZF) proteins are transcription regulators with roles in development, differentiation, and oncogenesis. In these proteins, the BTB domain (also known as the POZ domain) is a protein-protein interaction motif that contains a dimerization interface, a possible oligomerization surface, and surfaces for interactions with other factors, including nuclear co-repressors and histone deacetylases. The BTB-ZF protein LRF (also known as ZBTB7, FBI-1, OCZF, and Pokemon) is a master regulator of oncogenesis, and represses the transcription of a variety of important genes, including the ARF, c-fos, and c-myc oncogenes and extracellular matrix genes. We determined the crystal structure of the BTB domain from human LRF to 2.1 angstrom and observed the canonical BTB homodimer fold. However, novel features are apparent on the surface of the homodimer, including differences in the lateral groove and charged pocket regions. The residues that line the lateral groove have little similarity with the equivalent residues from the BCL6 BTB domain, and we show that the 17-residue BCL6 Binding Domain (BBD) from the SMRT co-repressor does not bind to the LRF BTB domain.