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


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.

SUBMITTER: Veverka P 

PROVIDER: S-EPMC9860152 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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

Veverka Pavel P   Brom Tomáš T   Janovič Tomáš T   Stojaspal Martin M   Pinkas Matyáš M   Nováček Jiří J   Hofr Ctirad C  

Computational and structural biotechnology journal 20221219


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 a  ...[more]

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