Genetically encoded formaldehyde sensors inspired by a protein intra-helical crosslinking reaction

Rongfeng Zhu, Gong Zhang, Miao Jing, Yu Han, Jiaofeng Li, Jingyi Zhao, Yulong Li and Peng R. Chen ()
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Rongfeng Zhu: Peking University
Gong Zhang: Peking University
Miao Jing: Peking-Tsinghua Center for Life Sciences
Yu Han: Peking University
Jiaofeng Li: Peking University
Jingyi Zhao: Peking University
Yulong Li: Peking-Tsinghua Center for Life Sciences
Peng R. Chen: Peking University

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20754-4

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DOI: 10.1038/s41467-020-20754-4

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