Abstract
AbstractFormaldehyde (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.
Funder
National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
Reference62 articles.
1. Kalasz, H. Biological role of formaldehyde, and cycles related to methylation, demethylation, and formaldehyde production. Mini Rev. Med. Chem. 3, 175–192 (2003).
2. Boomsma, F., Hut, H., Bhaggoe, U., van der Houwen, A. & van den Meiracker, A. Semicarbazide-sensitive amine oxidase (SSAO): from cell to circulation. Med. Sci. Monit. 11, Ra122–Ra126 (2005).
3. Walport, L. J., Hopkinson, R. J. & Schofield, C. J. Mechanisms of human histone and nucleic acid demethylases. Curr. Opin. Chem. Biol. 16, 525–534 (2012).
4. Garaycoechea, J. I. et al. Genotoxic consequences of endogenous aldehydes on mouse haematopoietic stem cell function. Nature 489, 571–575 (2012).
5. Pontel, L. B. et al. Endogenous formaldehyde is a hematopoietic stem cell genotoxin and metabolic carcinogen. Mol. Cell 60, 177–188 (2015).
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