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电子显微镜揭示了主要神经元细胞分化因子REST（RE1沉默转录因子）的环形结构。

Electron microscopy reveals toroidal shape of master neuronal cell differentiator REST - RE1-silencing transcription factor.

作者信息

Veverka Pavel, Brom Tomáš, Janovič Tomáš, Stojaspal Martin, Pinkas Matyáš, Nováček Jiří, Hofr Ctirad

机构信息

LifeB, FGP - NCBR, Faculty of Science, Masaryk University, Kamenice 753/5, Brno 625 00, Czech Republic.

Institute of Biophysics of the Czech Academy of Sciences, Scientific Incubator, Královopolská 135, Brno 612 65, Czech Republic.

出版信息

Comput Struct Biotechnol J. 2022 Dec 19;21:731-741. doi: 10.1016/j.csbj.2022.12.026. eCollection 2023.

DOI:10.1016/j.csbj.2022.12.026
PMID:36698979
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9860152/
Abstract

The RE1-Silencing Transcription factor (REST) is essential for neuronal differentiation. Here, we report the first 18.5-angstrom electron microscopy structure of human REST. The refined electron map suggests that REST forms a torus that can accommodate DNA double-helix in the central hole. Additionally, we quantitatively described REST binding to the canonical DNA sequence of the neuron-restrictive silencer element. We developed protocols for the expression and purification of full-length REST and the shortened variant REST-N62 produced by alternative splicing. We tested the mutual interaction of full-length REST and the splicing variant REST-N62. Revealed structure-function relationships of master neuronal repressor REST will allow finding new biological ways of prevention and treatment of neurodegenerative disorders and diseases.

摘要

RE1沉默转录因子（REST）对神经元分化至关重要。在此，我们报告了人类REST的首个18.5埃电子显微镜结构。优化后的电子密度图表明，REST形成了一个环面，其中心孔可容纳DNA双螺旋。此外，我们定量描述了REST与神经元限制性沉默元件的典型DNA序列的结合。我们开发了全长REST以及由可变剪接产生的缩短变体REST-N62的表达和纯化方案。我们测试了全长REST与剪接变体REST-N62之间的相互作用。揭示主神经元抑制因子REST的结构-功能关系将有助于找到预防和治疗神经退行性疾病的新生物学方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa5/9860152/e5ec714c72b2/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa5/9860152/50d7bb5dcc49/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa5/9860152/c4e168251764/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa5/9860152/d84be02e9560/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa5/9860152/7bf56ec2a65f/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa5/9860152/4c76e03eea97/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa5/9860152/d6fa19ea21fe/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa5/9860152/c7aaae429320/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa5/9860152/0bf9eced451b/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa5/9860152/e5ec714c72b2/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa5/9860152/50d7bb5dcc49/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa5/9860152/c4e168251764/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa5/9860152/d84be02e9560/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa5/9860152/7bf56ec2a65f/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa5/9860152/4c76e03eea97/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa5/9860152/d6fa19ea21fe/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa5/9860152/c7aaae429320/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa5/9860152/0bf9eced451b/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa5/9860152/e5ec714c72b2/gr8.jpg

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