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Triblock Proteins with Weakly Dimerizing Terminal Blocks and an Intrinsically Disordered Region for Rational Design of Condensate Properties

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A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

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en

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9

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Small, Volume 20, issue 13

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Condensates are molecular assemblies that are formed through liquid–liquid phase separation and play important roles in many biological processes. The rational design of condensate formation and their properties is central to applications, such as biosynthetic materials, synthetic biology, and for understanding cell biology. Protein engineering is used to make a triblock structure with varying terminal blocks of folded proteins on both sides of an intrinsically disordered mid-region. Dissociation constants are determined in the range of micromolar to millimolar for a set of proteins suitable for use as terminal blocks. Varying the weak dimerization of terminal blocks leads to an adjustable tendency for condensate formation while keeping the intrinsically disordered region constant. The dissociation constants of the terminal domains correlate directly with the tendency to undergo liquid–liquid phase separation. Differences in physical properties, such as diffusion rate are not directly correlated with the strength of dimerization but can be understood from the properties and interplay of the constituent blocks. The work demonstrates the importance of weak interactions in condensate formation and shows a principle for protein design that will help in fabricating functional condensates in a predictable and rational way.

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Funding Information: The authors acknowledge the provision of facilities by the Bioeconomy Infrastructure and the RAMI—RawMatters Finland Infrastructure at Aalto University and the computational resources by the CSC IT Centre for Finland. MSc Yin Yin and MSc Ellinor Englund are thanked for their help with the cloning of recombinant proteins. This work was supported by the Academy of Finland through projects #317395 and #333238, the Center of Excellence Program (2022‐2029) in Life‐Inspired Hybrid Materials (LIBER) (projects #346105 and #346111), and the Novo Nordisk Foundation (#NNF20OC0061306, #NNF23OC0081564, and #NNF22OC0074060). Publisher Copyright: © 2023 The Authors. Small published by Wiley-VCH GmbH.

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Fedorov, D, Roas-Escalona, N, Tolmachev, D, Harmat, A L, Scacchi, A, Sammalkorpi, M, Aranko, A S & Linder, M B 2024, 'Triblock Proteins with Weakly Dimerizing Terminal Blocks and an Intrinsically Disordered Region for Rational Design of Condensate Properties', Small, vol. 20, no. 13, 2306817. https://doi.org/10.1002/smll.202306817

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