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

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Authors

VEVERKA Pavel BROM Tomáš JANOVIČ Tomáš STOJASPAL Martin PINKAS Matyáš NOVÁČEK Jiří HOFR Ctirad

Year of publication 2023
Type Article in Periodical
Magazine / Source Computational and Structural Biotechnology Journal
MU Faculty or unit

Faculty of Science

Citation
web https://www.sciencedirect.com/science/article/pii/S2001037022005827
Doi http://dx.doi.org/10.1016/j.csbj.2022.12.026
Keywords REST; RE1-silencing transcription factor; Neuron-restrictive silencer factor; Neuronal Differentiation; REST-N62; REST4; NRSF; EM; Electron microscopy
Attached files
Description 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.
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