Chemical probes for investigating protein liquid-liquid phase separation and aggregation

Sun, Rui; Zhang, Shenqing; Liu, Yu; Li, Dan

doi:10.1016/j.cbpa.2023.102291

Current Opinion in Chemical Biology

2023

DOI: 10.1016/j.cbpa.2023.102291

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Chemical probes for investigating protein liquid-liquid phase separation and aggregation

Rui Sun

Shenqing Zhang

Yu Liu

et al.

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Cited by 5 publications

References 59 publications

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A Cell‐Permeable Photosensitizer for Selective Proximity Labeling and Crosslinking of Aggregated Proteome

Feng,

Zhao,

Zhao

et al. 2024

Advanced Science

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Intracellular proteome aggregation is a ubiquitous disease hallmark with its composition associated with pathogenicity. Herein, this work reports on a cell‐permeable photosensitizer (P8, Rose Bengal derivative) for selective photo induced proximity labeling and crosslinking of cellular aggregated proteome. Rose Bengal is identified out of common photosensitizer scaffolds for its unique intrinsic binding affinity to various protein aggregates driven by the hydrophobic effect. Further acetylation permeabilizes Rose Bengal to selectively image, label, and crosslink aggregated proteome in live stressed cells. A combination of photo‐chemical, tandem mass spectrometry, and protein biochemistry characterizations reveals the complexity in photosensitizing pathways (both Type I & II), modification sites and labeling mechanisms. The diverse labeling sites and reaction types result in highly effective enrichment and identification of aggregated proteome. Finally, aggregated proteomics and interaction analyses thereby reveal extensive entangling of proteostasis network components mediated by HSP70 chaperone (HSPA1B) and active participation of autophagy pathway in combating proteasome inhibition. Overall, this work exemplifies the first photo induced proximity labeling and crosslinking method (namely AggID) to profile intracellular aggregated proteome and analyze its interactions.

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A Cell‐Permeable Photosensitizer for Selective Proximity Labeling and Crosslinking of Aggregated Proteome

Feng,

Zhao,

Zhao

et al. 2024

Advanced Science

Self Cite

View full text Add to dashboard Cite

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Protein phase separation disorder as a potentially pervasive pathogenic mechanism of male infertility

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Chemical probes for investigating protein liquid-liquid phase separation and aggregation

Cited by 5 publications

References 59 publications

A Cell‐Permeable Photosensitizer for Selective Proximity Labeling and Crosslinking of Aggregated Proteome

A Cell‐Permeable Photosensitizer for Selective Proximity Labeling and Crosslinking of Aggregated Proteome

Protein phase separation disorder as a potentially pervasive pathogenic mechanism of male infertility

Liquid-liquid phase separation in human diseases: Functions, mechanisms and treatments

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