Structural details of the OxyR peroxide-sensing mechanism

Abstract

Significance In gram-negative bacteria, OxyR is the master peroxide sensor that regulates the transcription of defense genes in response to a low level of cellular H 2 O 2 via a rapid kinetic reaction. In this study, we present the first, to our knowledge, full-length structures of peroxide-sensing transcription regulator OxyR together with an oxidation intermediate-mimicking structure. The structures show all of the structural features describing the tetrameric assembly and a bound H 2 O 2 molecule near the conserved cysteine. Combining the structural results, we reveal a step-by-step molecular mechanism for OxyR from H 2 O 2 sensing to structural changes for transcriptional activation. Our study provides a structural basis for potentially answering key questions about the role of the cysteine residue in other Cys-based sensors, even mammalian ones, in response to various oxidants.