Crystal structure of the BTB domain from PLZF
Crystal structure of the BTB domain from PLZF
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DOI：
10.1073/pnas.95.21.12123
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发表时间：
1998-10-13
影响因子：
11.1
通讯作者：
Privé, GG
中科院分区：
文献类型：
--
作者：
Ahmad, KF;Engel, CK;Privé, GG
BTB结构域（也称为POZ结构域）是一种进化上保守的蛋白质-蛋白质相互作用基序，存在于5-10%的C2 H2型锌指转录因子的N末端，以及一些带有kelch基序的肌动蛋白相关蛋白中。许多BTB蛋白是通过控制染色质构象来介导基因表达的转录调节因子。在人早幼粒细胞白血病锌指（PLZF）蛋白中，BTB结构域具有转录抑制活性，将蛋白质引导至核点状模式，并与组蛋白脱乙酰酶复合物的组分相互作用。PLZF BTB结构域与组蛋白脱乙酰酶复合物的结合提供了将转录因子与调节染色质构象的酶活性连接的机制。PLZF的BTB结构域的晶体结构在1.9埃分辨率下测定，并揭示了具有广泛疏水界面的紧密缠绕的二聚体。大约四分之一的单体表面积参与二聚体分子间接触。这些特征是专性同二聚体的典型特征，我们预计全长PLZF蛋白将作为具有两个C末端DNA结合区的分支转录因子存在。在二聚体界面处形成衬有保守氨基酸的表面暴露凹槽，提示肽结合位点。该沟可能代表PLZF BTB结构域与核辅阻遏物或其他核蛋白相互作用的位点。
The BTB domain (also known as the POZ domain) is an evolutionarily conserved protein-protein interaction motif found at the N terminus of 5-10% of C2H2-type zinc-finger transcription factors, as well as in some actin-associated proteins bearing the kelch motif. Many BTB proteins are transcriptional regulators that mediate gene expression through the control of chromatin conformation. In the human promyelocytic leukemia zinc finger (PLZF) protein, the BTB domain has transcriptional repression activity, directs the protein to a nuclear punctate pattern, and interacts with components of the histone deacetylase complex. The association of the PLZF BTB domain with the histone deacetylase complex provides a mechanism of linking the transcription factor with enzymatic activities that regulate chromatin conformation. The crystal structure of the BTB domain of PLZF was determined at 1.9 Angstrom resolution and reveals a tightly intertwined dimer with an extensive hydrophobic interface. Approximately one-quarter of the monomer surface area is involved in the dimer intermolecular contact. These features are typical of obligate homodimers, and we expect the full-length PLZF protein to exist as a branched transcription factor with two C-terminal DNA-binding regions. A surface-exposed groove lined with conserved amino acids is formed at the dimer interface, suggestive of a peptide-binding site. This groove may represent the site of interaction of the PLZF BTB domain with nuclear corepressors or other nuclear proteins.