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Phase separation propensity of the intrinsically disordered AB region of human RXRβ

RXRβ is one of three subtypes of human retinoid X receptor (RXR), a transcription factor that belongs to the nuclear receptor superfamily. Its expression can be detected in almost all tissues. In contrast to other subtypes – RXRα and RXRγ – RXRβ has the longest and unique N-terminal sequence called...

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Autores principales: Sołtys, Katarzyna, Ożyhar, Andrzej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10157963/
https://www.ncbi.nlm.nih.gov/pubmed/37143076
http://dx.doi.org/10.1186/s12964-023-01113-4
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author Sołtys, Katarzyna
Ożyhar, Andrzej
author_facet Sołtys, Katarzyna
Ożyhar, Andrzej
author_sort Sołtys, Katarzyna
collection PubMed
description RXRβ is one of three subtypes of human retinoid X receptor (RXR), a transcription factor that belongs to the nuclear receptor superfamily. Its expression can be detected in almost all tissues. In contrast to other subtypes – RXRα and RXRγ – RXRβ has the longest and unique N-terminal sequence called the AB region, which harbors a ligand-independent activation function. In contrast to the functional properties of this sequence, the molecular properties of the AB region of human RXRβ (AB_hRXRB) have not yet been characterized. Here, we present a systematic biochemical and biophysical analysis of recombinant AB_hRXRB, along with in silico examinations, which demonstrate that AB_hRXRB exhibits properties of a coil-like intrinsically disordered region. AB_hRXRB possesses a flexible structure that is able to adopt a more ordered conformation under the influence of different environmental factors. Interestingly, AB_hRXRB promotes the formation of liquid–liquid phase separation (LLPS), a phenomenon previously observed for the AB region of another human subtype of RXR – RXRγ (AB_hRXRG). Although both AB regions seem to be similar in terms of their ability to induce phase separation, they clearly differ in the sensitivity to factors driving and regulating LLPS. This distinct LLPS response to environmental factors driven by the unique amino acid compositions of AB_hRXRB and AB_hRXRG can be significant for the specific modulation of the transcriptional activation of target genes by different subtypes of RXR. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12964-023-01113-4.
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spelling pubmed-101579632023-05-05 Phase separation propensity of the intrinsically disordered AB region of human RXRβ Sołtys, Katarzyna Ożyhar, Andrzej Cell Commun Signal Research RXRβ is one of three subtypes of human retinoid X receptor (RXR), a transcription factor that belongs to the nuclear receptor superfamily. Its expression can be detected in almost all tissues. In contrast to other subtypes – RXRα and RXRγ – RXRβ has the longest and unique N-terminal sequence called the AB region, which harbors a ligand-independent activation function. In contrast to the functional properties of this sequence, the molecular properties of the AB region of human RXRβ (AB_hRXRB) have not yet been characterized. Here, we present a systematic biochemical and biophysical analysis of recombinant AB_hRXRB, along with in silico examinations, which demonstrate that AB_hRXRB exhibits properties of a coil-like intrinsically disordered region. AB_hRXRB possesses a flexible structure that is able to adopt a more ordered conformation under the influence of different environmental factors. Interestingly, AB_hRXRB promotes the formation of liquid–liquid phase separation (LLPS), a phenomenon previously observed for the AB region of another human subtype of RXR – RXRγ (AB_hRXRG). Although both AB regions seem to be similar in terms of their ability to induce phase separation, they clearly differ in the sensitivity to factors driving and regulating LLPS. This distinct LLPS response to environmental factors driven by the unique amino acid compositions of AB_hRXRB and AB_hRXRG can be significant for the specific modulation of the transcriptional activation of target genes by different subtypes of RXR. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12964-023-01113-4. BioMed Central 2023-05-04 /pmc/articles/PMC10157963/ /pubmed/37143076 http://dx.doi.org/10.1186/s12964-023-01113-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Sołtys, Katarzyna
Ożyhar, Andrzej
Phase separation propensity of the intrinsically disordered AB region of human RXRβ
title Phase separation propensity of the intrinsically disordered AB region of human RXRβ
title_full Phase separation propensity of the intrinsically disordered AB region of human RXRβ
title_fullStr Phase separation propensity of the intrinsically disordered AB region of human RXRβ
title_full_unstemmed Phase separation propensity of the intrinsically disordered AB region of human RXRβ
title_short Phase separation propensity of the intrinsically disordered AB region of human RXRβ
title_sort phase separation propensity of the intrinsically disordered ab region of human rxrβ
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10157963/
https://www.ncbi.nlm.nih.gov/pubmed/37143076
http://dx.doi.org/10.1186/s12964-023-01113-4
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