A Divalent Ion Is Crucial in the Structure and Dominant-Negative Function of ID Proteins, a Class of Helix-Loop-Helix Transcription Regulators

被引:18
|
作者
Wong, Marie Vivian [1 ,2 ]
Jiang, Sizun [1 ]
Palasingam, Paaventhan [1 ]
Kolatkar, Prasanna R. [1 ,2 ]
机构
[1] Genome Inst Singapore, Lab Struct Biochem, Singapore, Singapore
[2] Natl Univ Singapore, Dept Biol Sci, Singapore 117548, Singapore
来源
PLOS ONE | 2012年 / 7卷 / 10期
关键词
DNA-BINDING; CELL-CYCLE; E-BOX; DOMAIN; RECOGNITION; INHIBITION; EXPRESSION; COMPLEXES; SOFTWARE; DISTINCT;
D O I
10.1371/journal.pone.0048591
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Inhibitors of DNA binding and differentiation (ID) proteins, a dominant-negative group of helix-loop-helix (HLH) transcription regulators, are well-characterized key players in cellular fate determination during development in mammals as well as Drosophila. Although not oncogenes themselves, their upregulation by various oncogenic proteins (such as Ras, Myc) and their inhibitory effects on cell cycle proteins (such as pRb) hint at their possible roles in tumorigenesis. Furthermore, their potency as inhibitors of cellular differentiation, through their heterodimerization with subsequent inactivation of the ubiquitous E proteins, suggest possible novel roles in engineering induced pluripotent stem cells (iPSCs). We present the high-resolution 2.1 angstrom crystal structure of ID2 (HLH domain), coupled with novel biochemical insights in the presence of a divalent ion, possibly calcium (Ca2+), in the loop of ID proteins, which appear to be crucial for the structure and activity of ID proteins. These new insights will pave the way for new rational drug designs, in addition to current synthetic peptide options, against this potent player in tumorigenesis as well as more efficient ways for stem cells reprogramming.
引用
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页数:10
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