Tandem-repeat proteins introduce tuneable properties to engineered biomolecular condensates
Year: 2025
Type: article
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 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.
Source: Chemical Science
DOI: 10.1039/d5sc00903k
Institutions: University of Cambridge, Princeton University
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
Funders: Princeton University, Frances and Augustus Newman Foundation, UK Research and Innovation, Royal Society, European Commission, Rosetrees Trust, Human Frontier Science Program, Medical Research Council, Engineering and Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council, H2020 European Research Council, H2020 Marie Skłodowska-Curie Actions
Awards: MicroREvolution - a high-throughput drop-based microfluidic platform for rapid screening of highly diverse antimicrobial peptide mutant libraries generated via directed evolution., G1269401263, MicroREvolution - a high-throughput drop-based microfluidic platform for rapid screening of highly diverse antimicrobial peptide mutant libraries generated via directed evolution., G3105972059, G3202580820, The UK High-End Computing Consortium for Biomolecular Simulation, G3835265546, G434337789, Computational modelling of DNA compartmentalization via liquid-liquid phase separation, G7342468323, Towards Realistic Modelling of Nucleosome Organization Inside Functional Chromatin Domains, Establishing a structure-function relationship between biomolecular condensates and protein degradation
OpenAlex ID: W4410099365