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

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. Additiona...

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Detalles Bibliográficos
Autores principales: Veverka, Pavel, Brom, Tomáš, Janovič, Tomáš, Stojaspal, Martin, Pinkas, Matyáš, Nováček, Jiří, Hofr, Ctirad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Research Network of Computational and Structural Biotechnology 2022
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9860152/
https://www.ncbi.nlm.nih.gov/pubmed/36698979
http://dx.doi.org/10.1016/j.csbj.2022.12.026
Descripción
Sumario: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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