SNAP output for PDB entry 7bzg [SNAP web server]

PDB-id

7bzg; SNAP-derived features in text and JSON formats; DNAproDB

Class

DNA binding protein

Method

X-ray (2.9 Å)

Summary

Structure of bacillus subtilis hxlr, wild type in complex with formaldehyde and DNA

Reference

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

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.