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肽生物分子凝聚物的化学成分对酶促反应的调节。

Regulation of enzymatic reactions by chemical composition of peptide biomolecular condensates.

作者信息

Harris Rif, Veretnik Shirel, Dewan Simran, Baruch Leshem Avigail, Lampel Ayala

机构信息

Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.

Center for Nanoscience and Nanotechnology Tel Aviv University, Tel Aviv, 69978, Israel.

出版信息

Commun Chem. 2024 Apr 20;7(1):90. doi: 10.1038/s42004-024-01174-7.

DOI:10.1038/s42004-024-01174-7
PMID:38643237
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11032315/
Abstract

Biomolecular condensates are condensed intracellular phases that are formed by liquid-liquid phase separation (LLPS) of proteins, either in the absence or presence of nucleic acids. These condensed phases regulate various biochemical reactions by recruitment of enzymes and substrates. Developments in the field of LLPS facilitated new insights on the regulation of compartmentalized enzymatic reactions. Yet, the influence of condensate chemical composition on enzymatic reactions is still poorly understood. Here, by using peptides as minimalistic condensate building blocks and β-galactosidase as a simple enzymatic model we show that the reaction is restricted in homotypic peptide condensates, while product formation is enhanced in peptide-RNA condensates. Our findings also show that condensate composition affects the recruitment of substrate, the spatial distribution, and the kinetics of the reaction. Thus, these findings can be further employed for the development of microreactors for biotechnological applications.

摘要

生物分子凝聚物是通过蛋白质的液-液相分离(LLPS)形成的凝聚细胞内相,无论有无核酸存在。这些凝聚相通过招募酶和底物来调节各种生化反应。LLPS领域的发展促进了对区室化酶促反应调控的新认识。然而,凝聚物化学成分对酶促反应的影响仍知之甚少。在这里,通过使用肽作为简约的凝聚物构建块,并以β-半乳糖苷酶作为简单的酶模型,我们表明该反应在同型肽凝聚物中受到限制,而在肽-RNA凝聚物中产物形成增强。我们的研究结果还表明,凝聚物组成会影响底物的招募、空间分布和反应动力学。因此,这些发现可进一步用于开发用于生物技术应用的微反应器。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e630/11032315/11c3ce0ab91a/42004_2024_1174_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e630/11032315/1da7c7b724e1/42004_2024_1174_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e630/11032315/615bdf4768ad/42004_2024_1174_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e630/11032315/8d4ef8babaa4/42004_2024_1174_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e630/11032315/5962bdcbb295/42004_2024_1174_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e630/11032315/891600cb2dad/42004_2024_1174_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e630/11032315/11c3ce0ab91a/42004_2024_1174_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e630/11032315/1da7c7b724e1/42004_2024_1174_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e630/11032315/615bdf4768ad/42004_2024_1174_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e630/11032315/8d4ef8babaa4/42004_2024_1174_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e630/11032315/5962bdcbb295/42004_2024_1174_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e630/11032315/891600cb2dad/42004_2024_1174_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e630/11032315/11c3ce0ab91a/42004_2024_1174_Fig6_HTML.jpg

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本文引用的文献

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2
Modulating the optical properties of carbon dots by peptide condensates.通过肽缩合物调节碳点的光学性质。
Chem Commun (Camb). 2023 Oct 12;59(82):12298-12301. doi: 10.1039/d3cc03945e.
3
Biomolecular condensates formed by designer minimalistic peptides.由设计的极简肽形成的生物分子凝聚物。
为先进生物技术应用定制肽凝聚层:增强控制、封装和抗氧化性能
ACS Appl Mater Interfaces. 2025 May 28;17(21):31561-31574. doi: 10.1021/acsami.5c02367. Epub 2025 Apr 28.
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Coacervates as enzymatic microreactors.凝聚层作为酶促微反应器。
Chem Soc Rev. 2025 May 6;54(9):4183-4199. doi: 10.1039/d4cs01203h.
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Recombinase-Controlled Multiphase Condensates Accelerate Nucleic Acid Amplification and CRISPR-Based Diagnostics.重组酶控制的多相凝聚物加速核酸扩增和基于CRISPR的诊断。
J Am Chem Soc. 2025 Mar 26;147(12):10088-10103. doi: 10.1021/jacs.4c11893. Epub 2025 Feb 13.
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