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Low amounts of heavy water increase the phase separation propensity of a fragment of the androgen receptor activation domain.

ABSTRACT: The phase equilibria of intrinsically disordered proteins are exquisitely sensitive to changes in solution conditions and this can be used to investigate the driving forces of phase separation in vitro as well as the biological roles of phase transitions in live cells. Here we investigate how using D₂ O as co-solvent in an aqueous buffer changes the phase equilibrium of a fragment of the activation domain of the androgen receptor, a transcription factor that plays a role in the development of the male phenotype and is a therapeutic target for castration resistant prostate cancer. We show how replacing even small fractions of H₂ O with D₂ O increases the propensity of this fragment to undergo liquid-liquid phase separation, likely reflecting a stabilization of the hydrophobic interactions that drive condensation. Our results indicate that it is necessary to take this effect into consideration when studying phase separation phenomena with biophysical methods that require using D₂ O as a co-solvent. In addition, they suggest that additions of D₂ O may be used to enhance phase separation phenomena in cells, facilitating their observation.

SUBMITTER: Bielskute S

PROVIDER: S-EPMC8197436 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Low amounts of heavy water increase the phase separation propensity of a fragment of the androgen receptor activation domain.

Bielskutė Stasė S Garcia-Cabau Carla C Frigolé-Vivas Marta M Szulc Elzbieta E De Mol Eva E Pesarrodona Mireia M García Jesús J Salvatella Xavier X

Protein science : a publication of the Protein Society 20210524 7

The phase equilibria of intrinsically disordered proteins are exquisitely sensitive to changes in solution conditions and this can be used to investigate the driving forces of phase separation in vitro as well as the biological roles of phase transitions in live cells. Here we investigate how using D<sub>2</sub> O as co-solvent in an aqueous buffer changes the phase equilibrium of a fragment of the activation domain of the androgen receptor, a transcription factor that plays a role in the develo ...[more]

PMID: 33978290

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Low amounts of heavy water increase the phase separation propensity of a fragment of the androgen receptor activation domain.

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Low amounts of heavy water increase the phase separation propensity of a fragment of the androgen receptor activation domain.

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