Structural basis for the dimerization mechanism of human transcription factor E3
Structural basis for the dimerization mechanism of human transcription factor E3
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人转录因子E3二聚化机制的结构基础
DOI：
10.1016/j.bbrc.2021.06.091
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发表时间：
2021
影响因子：
3.1
通讯作者：
Wang Jing
中科院分区：
文献类型：
--
作者：
Yang Guang;Li Peifeng;Liu Zaizhou;Wu Siqi;Zhuang Chen;Qiao Hang;Zheng Li;Fang Pengfei;Lei Chuanhu;Wang Jing
免疫球蛋白重链增强子3（TFE 3）转录因子是小眼症（MiT/TFE）转录因子家族的成员。由于染色体异常导致的TFE 3失调与一部分人肾细胞癌相关这一关键转录因子的结构信息很少有报道。在这项研究中，我们确定了人TFE 3的螺旋-环-螺旋亮氨酸拉链（HLH-Lz）结构域的晶体结构，分辨率为2.6 μ m。HLH-Lz结构域对于TFE 3的二聚化和功能至关重要。我们的结构表明，保守的HLH区域形成了一个四螺旋束结构，主要是疏水性的核心，和亮氨酸拉链区域有助于TFE 3的功能，促进二聚体相互作用，并提供合作伙伴的选择性。总之，我们的研究结果阐明了这种重要的转录因子的二聚化机制，为治疗TFE 3失调疾病的抑制策略的发展提供了结构基础。
The transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3) is a member of the microphthalmia (MiT/TFE) transcription factor family. Dysregulation of TFE3 due to chromosomal abnormalities is associated with a subset of human renal cell carcinoma. Little structural information of this key transcription factor has been reported. In this study, we determined the crystal structure of the helix-loop-helix leucine zipper (HLH-Lz) domain of human TFE3 to a resolution of 2.6 Å. The HLH-Lz domain is critical for the dimerization and function of TFE3. Our structure showed that the conserved HLH region formed a four-helix bundle structure with a predominantly hydrophobic core, and the leucine zipper region contributed to the function of TFE3 by promoting dimer interaction and providing partner selectivity. Together, our results elucidated the dimerization mechanism of this important transcription factor, providing the structural basis for the development of inhibiting strategies for treating TFE3 dysregulated diseases.