Ordered structure-forming properties of the intrinsically disordered AB region of hRXRγ and its ability to promote liquid-liquid phase separation

Sołtys, Katarzyna; Ożyhar, Andrzej

doi:10.1016/j.jsbmb.2019.105571

Cited by 12 publications

(14 citation statements)

References 77 publications

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“…In particular, the formation of AR and PPARγ liquid condensates is mediated by DBD [ 23 , 24 ], whereas GR is mediated by LBD [ 25 ]. On the other hand, for the estrogen receptor (ER) and RXRγ, AB regions seem to be essential for condensate formation [ 26 , 27 ]. Additionally, LLPS of RXRγ is driven by hydrophobic interactions, which is quite an unusual feature for IDRs [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

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

Sołtys

Ożyhar

2023

Cell Commun Signal

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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.

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Section: Introductionmentioning

confidence: 99%

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

Sołtys

Ożyhar

2023

Cell Commun Signal

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“…To our knowledge, only the NTD of the human RXRγ has been described to form liquid droplets in vitro in the absence of other proteins. 284 For the previously mentioned ER case, liquid droplets were observed in the presence of the coactivator MED1 NRID, containing the LXXLL motifs. Interestingly, in the presence of the agonist (estrogen) the incorporation of the ER into the MED1 droplets is enhanced.…”

Section: Liquid-liquid Phase Separation (Llps) In Nrsmentioning

confidence: 93%

IDPs and their complexes in GPCR and nuclear receptor signaling

Guillien¹,

Maire²,

Mouhand³

et al. 2020

Progress in Molecular Biology and Translational Science

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“…An intrinsically disordered AB region of h RXRγ seems to be responsible for LLPS of this receptor. It was shown that this region forms condensates in vitro in the absence of other proteins [ 88 ]. These condensates are able to incorporate the remaining fragment of the receptor into the droplets.…”

Section: Transcription Regulators and Liquid–liquid Phase Separationmentioning

confidence: 99%

Transcription Regulators and Membraneless Organelles Challenges to Investigate Them

Sołtys

Ożyhar

2021

IJMS

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Eukaryotic cells are composed of different bio-macromolecules that are divided into compartments called organelles providing optimal microenvironments for many cellular processes. A specific type of organelles is membraneless organelles. They are formed via a process called liquid–liquid phase separation that is driven by weak multivalent interactions between particular bio-macromolecules. In this review, we gather crucial information regarding different classes of transcription regulators with the propensity to undergo liquid–liquid phase separation and stress the role of intrinsically disordered regions in this phenomenon. We also discuss recently developed experimental systems for studying formation and properties of membraneless organelles.

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Ordered structure-forming properties of the intrinsically disordered AB region of hRXRγ and its ability to promote liquid-liquid phase separation

Cited by 12 publications

References 77 publications

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

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

IDPs and their complexes in GPCR and nuclear receptor signaling

Transcription Regulators and Membraneless Organelles Challenges to Investigate Them

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