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Structural basis for the dimerization mechanism of human transcription factor E3.

Authors :
Yang, Guang
Li, Peifeng
Liu, Zaizhou
Wu, Siqi
Zhuang, Chen
Qiao, Hang
Zheng, Li
Fang, Pengfei
Lei, Chuanhu
Wang, Jing
Source :
Biochemical & Biophysical Research Communications. Sep2021, Vol. 569, p41-46. 6p.
Publication Year :
2021

Abstract

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. • TFE3 is a key transcription factor associated with a subset of human kidney cancer. • The crystal structure of the HLH-Lz domain of human TFE3 is determined. • The dimerization mechanism within HLH-Lz domain is analyzed. • We propose a possible strategy for inhibiting TFE3 activity. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
0006291X
Volume :
569
Database :
Academic Search Index
Journal :
Biochemical & Biophysical Research Communications
Publication Type :
Academic Journal
Accession number :
151832109
Full Text :
https://doi.org/10.1016/j.bbrc.2021.06.091