Genetically encoded formaldehyde sensors inspired by a protein intra-helical crosslinking reaction
Year: 2021
Type: article
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.
Source: Nature Communications
Institutions: Xiamen University, Peking University, Beijing National Laboratory for Molecular Sciences, Chongqing University, Chinese Institute for Brain Research, Center for Life Sciences, State Key Laboratory of Membrane Biology, Key Laboratory of Bioorganic Chemistry and Molecular Engineering, Ministry of Education
Language: English
Subfield: Biophysics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,560
OpenAlex ID: W3125375788