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原核和真核转录调节因子中与 p53 同源的四聚化结构域。

A tetramerization domain in prokaryotic and eukaryotic transcription regulators homologous to p53.

机构信息

Experiments Division, ALBA Synchrotron Light Source, Carrer de la Llum 2-26, 08290 Cerdanyola del Vallès, Catalunya, Spain.

Centro de Biología Molecular `Severo Ochoa' (CSIC-UAM), Universidad Autónoma de Madrid, Calle Nicolás Cabrera 1, Canto Blanco, 28049 Madrid, Spain.

出版信息

Acta Crystallogr D Struct Biol. 2023 Mar 1;79(Pt 3):259-267. doi: 10.1107/S2059798323001298.

DOI:10.1107/S2059798323001298
PMID:36876435
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9986798/
Abstract

Transcriptional regulation usually requires the action of several proteins that either repress or activate a promotor of an open reading frame. These proteins can counteract each other, thus allowing tight regulation of the transcription of the corresponding genes, where tight repression is often linked to DNA looping or cross-linking. Here, the tetramerization domain of the bacterial gene repressor Rco from Bacillus subtilis plasmid pLS20 (Rco) has been identified and its structure is shown to share high similarity to the tetramerization domain of the well known p53 family of human tumor suppressors, despite lacking clear sequence homology. In Rco, this tetramerization domain is responsible for inducing DNA looping, a process that involves multiple tetramers. In accordance, it is shown that Rco can form octamers. This domain was named TetD and its occurrence was identified in other Bacillus species. The TetD fold was also found in the structure of a transcriptional repressor from Salmonella phage SPC32H. It is proposed that the TetD fold has evolved through divergent evolution and that the TetD originates from a common ancestor predating the occurrence of multicellular life.

摘要

转录调控通常需要几种蛋白质的作用,这些蛋白质可以抑制或激活开放阅读框的启动子。这些蛋白质可以相互拮抗,从而实现对相应基因转录的紧密调控,其中紧密抑制通常与 DNA 环化或交联有关。在这里,已经鉴定出来自枯草芽孢杆菌质粒 pLS20(Rco)的细菌基因抑制剂 Rco 的四聚化结构域,并且其结构显示与众所周知的人类肿瘤抑制因子 p53 家族的四聚化结构域具有高度相似性,尽管缺乏明显的序列同源性。在 Rco 中,这个四聚化结构域负责诱导 DNA 环化,这是一个涉及多个四聚体的过程。因此,表明 Rco 可以形成八聚体。该结构域被命名为 TetD,并且在其他芽孢杆菌物种中也发现了其存在。在沙门氏菌噬菌体 SPC32H 的转录抑制剂的结构中也发现了 TetD 折叠。有人提出,TetD 折叠是通过分歧进化而来的,并且 TetD 起源于多细胞生命发生之前的共同祖先。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebfe/9986798/04b5836d6f79/d-79-00259-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebfe/9986798/d5bfe6d77bf3/d-79-00259-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebfe/9986798/2b7fd0ce07fa/d-79-00259-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebfe/9986798/04b5836d6f79/d-79-00259-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebfe/9986798/d5bfe6d77bf3/d-79-00259-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebfe/9986798/2b7fd0ce07fa/d-79-00259-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebfe/9986798/04b5836d6f79/d-79-00259-fig3.jpg

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Nature. 2021 Aug;596(7873):583-589. doi: 10.1038/s41586-021-03819-2. Epub 2021 Jul 15.
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Front Mol Biosci. 2021 Mar 18;8:648468. doi: 10.3389/fmolb.2021.648468. eCollection 2021.
3
Inactivation of the dimeric RappLS20 anti-repressor of the conjugation operon is mediated by peptide-induced tetramerization.
二聚体 RappLS20 抗阻遏物对接合操纵子的失活是由肽诱导的四聚化介导的。
Nucleic Acids Res. 2020 Aug 20;48(14):8113-8127. doi: 10.1093/nar/gkaa540.
4
Tumor Suppressor p53-Mediated Structural Reorganization of the Transcriptional Coactivator p300.肿瘤抑制因子 p53 介导的转录共激活因子 p300 的结构重排。
Biochemistry. 2019 Aug 13;58(32):3434-3443. doi: 10.1021/acs.biochem.9b00333. Epub 2019 Jul 31.
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Introduction to Genome Biology and Diversity.基因组生物学与多样性导论
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Correction: Brázda, V. and Coufal, J Recognition of Local DNA Structures by p53 Protein. 2017, , 375.更正:布拉兹达,V. 和库法尔,J. p53蛋白对局部DNA结构的识别。2017年,,375。
Int J Mol Sci. 2018 Sep 13;19(9):2737. doi: 10.3390/ijms19092737.
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