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Cited by 49Advanced Fluorescence Microscopy TechniquesBiochemical and Structural Characterizationbioluminescence and chemiluminescence research

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Genetically encoded formaldehyde sensors inspired by a protein intra-helical crosslinking reaction

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Zhu, Rongfeng, Zhang, Gong, Jing, Miao, Han, Yu, Li, Jiaofeng, Zhao, Jingyi, Li, Yulong, Chen, Peng R.·2021·Nature Communications
DOI 10.1038/s41467-020-20754-4PMC PMC7835342
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Abstract

Formaldehyde (FA) has long been considered as a toxin and carcinogen due to its damaging effects to biological macromolecules, but its beneficial roles have been increasingly appreciated lately. Real-time monitoring of this reactive molecule in living systems is highly desired in order to decipher its physiological and/or pathological functions, but a genetically encoded FA sensor is currently lacking. We herein adopt a structure-based study of the underlying mechanism of the FA-responsive transcription factor HxlR from Bacillus subtilis, which shows that HxlR recognizes FA through an intra-helical cysteine-lysine crosslinking reaction at its N-terminal helix α1, leading to conformational change and transcriptional activation. By leveraging this FA-induced intra-helical crosslinking and gain-of-function reorganization, we develop the genetically encoded, reaction-based FA sensor—FAsor, allowing spatial-temporal visualization of FA in mammalian cells and mouse brain tissues.

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  • Flow fiber photometry enables recordings from deep brain tissues and combined monitoring of blood and CSF dynamics using virally-delivered biosensors.

    “flow fiber photometry enables recordings from deep brain tissues and combined monitoring of blood and CSF dynamics using virally-delivered biosensors45,101–104.”

    From Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep (2025) · cites this paper as [103]

    The Results section, “Visualization of FA dynamics in mouse brain tissues by FAsors” (page unavailable), describes viral delivery of a fluorescent biosensor to the mouse hippocampus and imaging of formaldehyde responses in acute brain slices. It does not describe flow fiber photometry, recordings from deep brain tissue in vivo, or combined monitoring of blood and CSF dynamics. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Metadata

Authors
Zhu, R., Zhang, G., Jing, M., Han, Y., Li, J., Zhao, J., Li, Y., & Chen, P. R.
Affiliations
  • Xiamen University (CN)
  • Chongqing University (CN)
  • Peking University (CN)
Corresponding author
Chen, Peng R.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2021-01-25
Volume
12
Issue
1
Pages
581-581
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-020-20754-4
PMC
PMC7835342
OpenAlex
W3125375788
Cited by
49
References
1
Citations by year
2026: 5 · 2025: 10 · 2024: 7 · 2023: 7 · 2022: 14 · 2021: 6
FWCI
3.60
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (91753000)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › bioluminescence and chemiluminescence research
Keywords
formaldehyde sensing, genetically encoded biosensors, Bacillus subtilis, transcription factor activation, conformational change, live-cell imaging, mouse brain, reactive aldehydes
MeSH terms
Animals, Bacillus subtilis, Bacterial Proteins, Brain, Cross-Linking Reagents, Cysteine, Formaldehyde, Humans, Lysine, Protein Conformation, Transcription Factors, Reproducibility of Results, Biosensing Techniques, Mice

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