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分子间相互作用是蛋白质/肽相分离的基础，而与拥挤环境中的序列和结构无关。

Intermolecular interactions underlie protein/peptide phase separation irrespective of sequence and structure at crowded milieu.

机构信息

Department of Biosciences and Bioengineering, IIT Bombay, Powai, Mumbai, 400076, India.

Sunita Sanghi Centre of Aging and Neurodegenerative Diseases, IIT Bombay, Powai, Mumbai, 400076, India.

出版信息

Nat Commun. 2023 Oct 4;14(1):6199. doi: 10.1038/s41467-023-41864-9.

DOI:10.1038/s41467-023-41864-9
PMID:37794023
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10550955/
Abstract

Liquid-liquid phase separation (LLPS) has emerged as a crucial biological phenomenon underlying the sequestration of macromolecules (such as proteins and nucleic acids) into membraneless organelles in cells. Unstructured and intrinsically disordered domains are known to facilitate multivalent interactions driving protein LLPS. We hypothesized that LLPS could be an intrinsic property of proteins/polypeptides but with distinct phase regimes irrespective of their sequence and structure. To examine this, we studied many (a total of 23) proteins/polypeptides with different structures and sequences for LLPS study in the presence and absence of molecular crowder, polyethylene glycol (PEG-8000). We showed that all proteins and even highly charged polypeptides (under study) can undergo liquid condensate formation, however with different phase regimes and intermolecular interactions. We further demonstrated that electrostatic, hydrophobic, and H-bonding or a combination of such intermolecular interactions plays a crucial role in individual protein/peptide LLPS.

摘要

液-液相分离 (LLPS) 已成为一种重要的生物学现象，它将生物大分子（如蛋白质和核酸）隔离到细胞内的无膜细胞器中。无结构和固有无序的结构域被认为可以促进多价相互作用，从而驱动蛋白质的 LLPS。我们假设 LLPS 可能是蛋白质/多肽的固有特性，但具有不同的相态区域，而与它们的序列和结构无关。为了检验这一点，我们研究了许多（总共 23 种）具有不同结构和序列的蛋白质/多肽，以研究在存在和不存在分子拥挤剂聚乙二醇 (PEG-8000) 的情况下的 LLPS。我们表明，所有蛋白质，甚至是带高电荷的多肽（在研究中）都可以进行液体凝聚形成，但具有不同的相态区域和分子间相互作用。我们进一步证明，静电、疏水、氢键或这些分子间相互作用的组合在单个蛋白质/肽 LLPS 中起着关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3958/10550955/d35fe56fc762/41467_2023_41864_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3958/10550955/1f3c0cc45d3e/41467_2023_41864_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3958/10550955/3e7bfade5376/41467_2023_41864_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3958/10550955/bb0ff7fae93b/41467_2023_41864_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3958/10550955/9d9d04ed3f42/41467_2023_41864_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3958/10550955/348b4481492d/41467_2023_41864_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3958/10550955/65020efb107d/41467_2023_41864_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3958/10550955/d35fe56fc762/41467_2023_41864_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3958/10550955/1f3c0cc45d3e/41467_2023_41864_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3958/10550955/3e7bfade5376/41467_2023_41864_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3958/10550955/bb0ff7fae93b/41467_2023_41864_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3958/10550955/9d9d04ed3f42/41467_2023_41864_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3958/10550955/348b4481492d/41467_2023_41864_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3958/10550955/65020efb107d/41467_2023_41864_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3958/10550955/d35fe56fc762/41467_2023_41864_Fig8_HTML.jpg

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Proc Natl Acad Sci U S A. 2023 Feb 28;120(9):e2208792120. doi: 10.1073/pnas.2208792120. Epub 2023 Feb 21.
3
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4
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Protein Sci. 2025 Aug;34(8):e70232. doi: 10.1002/pro.70232.
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6
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