Electron Microscopy Reveals Toroidal Shape of Master Neuronal Cell Differentiator REST - RE1-silencing Transcription Factor

Overview

Journal Comput Struct Biotechnol J

Specialty Biotechnology

Date 2023 Jan 26

PMID 36698979

Authors

Pavel Veverka

Tomas Brom

Tomas Janovic

Martin Stojaspal

Matyas Pinkas

Jiri Novacek

Ctirad Hofr

Affiliations

Soon will be listed here.

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.

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