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Publication Abstract from PubMed

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 alpha1, 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.

Genetically encoded formaldehyde sensors inspired by a protein intra-helical crosslinking reaction.,Zhu R, Zhang G, Jing M, Han Y, Li J, Zhao J, Li Y, Chen PR Nat Commun. 2021 Jan 25;12(1):581. doi: 10.1038/s41467-020-20754-4. PMID:33495458^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.