Issue 23, 2025

Tandem-repeat proteins introduce tuneable properties to engineered biomolecular condensates

Abstract

The cell's ability to rapidly partition biomolecules into biomolecular condensates is linked to a diverse range of cellular functions. Understanding how the structural attributes of biomolecular condensates are linked with their biological roles can be facilitated by the development of synthetic condensate systems that can be manipulated in a controllable and predictable way. Here, we design and characterise a tuneable synthetic biomolecular condensate platform fusing modular consensus-designed tetratricopeptide repeat (CTPR) proteins to intrinsically-disordered domains. Trends between the CTPR structural attributes and condensate propensity were recapitulated across different experimental conditions and by in silico modelling, demonstrating that the CTPR domain can systematically affect the condensates in a predictable manner. Moreover, we show that incorporating short binding motifs into the CTPR domain results in specific target-protein recruitment into the condensates. Our model system can be rationally designed in a versatile manner to both tune condensate propensity and endow the condensates with new functions.

Graphical abstract: Tandem-repeat proteins introduce tuneable properties to engineered biomolecular condensates

Supplementary files

Article information

Article type
Edge Article
Submitted
04 Feb 2025
Accepted
04 May 2025
First published
05 May 2025
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2025,16, 10532-10548

Tandem-repeat proteins introduce tuneable properties to engineered biomolecular condensates

T. L. C. Ng, M. P. Hoare, M. J. Maristany, E. J. Wilde, T. Sneideris, J. Huertas, B. K. Agbetiameh, M. Furukawa, J. A. Joseph, T. P. J. Knowles, R. Collepardo-Guevara, L. S. Itzhaki and J. R. Kumita, Chem. Sci., 2025, 16, 10532 DOI: 10.1039/D5SC00903K

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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