1. Genetically encoded formaldehyde sensors inspired by a protein intra-helical crosslinking reaction
- Author
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Gong Zhang, Peng Chen, Yulong Li, Yu Han, Miao Jing, Jiaofeng Li, Jingyi Zhao, and Rongfeng Zhu
- 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 - 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.
- Published
- 2021