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Genetically encoded formaldehyde sensors inspired by a protein intra-helical crosslinking reaction
- Source :
- Nature Communications, Vol 12, Iss 1, Pp 1-13 (2021), Nature Communications
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
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.
- Subjects :
- 0301 basic medicine
Conformational change
Protein Conformation
Science
General Physics and Astronomy
Biosensing Techniques
Bacillus subtilis
010402 general chemistry
medicine.disease_cause
01 natural sciences
General Biochemistry, Genetics and Molecular Biology
Mice
03 medical and health sciences
Protein structure
Bacterial Proteins
Formaldehyde
medicine
Animals
Humans
Cysteine
Transcription factor
Sensors and probes
Carcinogen
Multidisciplinary
biology
Toxin
Chemistry
Lysine
Comment
Brain
Reproducibility of Results
General Chemistry
biology.organism_classification
0104 chemical sciences
Cell biology
Cross-Linking Reagents
Mechanisms of disease
030104 developmental biology
Helix
Transcription Factors
Macromolecule
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....55a5a85227fc369cde4b11e7d183712f