Microbes employ metalloprotein sensors to detect and respond to redox stresses in their environment. These sensors utilize metal cofactors to recognize specific redox stimuli and transmit the information downstream to modulate microbial metabolism. The focus of this article is to provide an overview of metalloprotein sensors that have been recently characterized. The article explores the metal coordination and oxidation state of the sensors, along with the signal transduction mechanisms that go beyond the metal center.The three types of metalloprotein sensors discussed are heme iron-based sensors, iron-sulfur cluster-based sensors, and nickel-iron cluster-based sensors.
Facts:
- 💡 Heme iron proteins are extensively studied as metalloprotein-based sensors.
- 💡 Heme sensors contain a heme cofactor coordinated to sidechains such as His, Cys, Met, or Pro.
- 💡 Different mechanisms are employed by heme sensors to recognize redox-active ligands.
- 💡 Redox events in heme sensors involve oxidation and coordination state changes of heme iron.
- 💡 The molecular mechanism of propagating the redox signal downstream in heme sensors is not fully understood.
- 💡 Metalloprotein sensors can transmit the signal through various mechanisms such as phosphorylation pathways, DNA binding, or metabolite production.
- 💡 Metalloprotein-based signal transduction pathways play a crucial role in microbial adaptation to changing environmental conditions.
Metalloprotein sensors, particularly heme iron-based sensors, are extensively studied due to their diverse roles in microbial adaptation. Heme sensors utilize a heme cofactor coordinated to specific sidechains within protein domains such as PAS, GAF, globin, or H-NOX. These sensors exhibit different mechanisms to recognize redox-active ligands. For example, heme sensors like DosS/DosT can transition between catalytically inactive and active forms upon binding to ligands such as NO or CO. Changes in the coordination state and oxidation state of the heme iron are crucial for signal recognition.
While the mechanisms of ligand recognition in heme sensors have been explored, the propagation of the redox signal downstream remains a subject of ongoing research. One well-studied system is the DosS heme sensor in mycobacteria, which undergoes autophosphorylation upon sensing NO or CO. The phosphorylated DosS interacts with the response regulator DosR, leading to the activation of dormancy-inducing genes.
Apart from histidine kinase/response regulator-based pathways, metalloprotein sensors can also transmit the signal downstream through direct DNA binding or the production of metabolites. For example, the CooA sensor facilitates transcription of CO oxidation machinery by exposing its DNA-binding region upon CO sensing. The Ec DosP sensor, upon O2 sensing, catalyzes the conversion of cyclic-di-GMP to linear di-GMP, enabling the bacterium to adapt to changing O2 concentrations.
The field of metalloprotein-based signal transduction pathways holds promise for understanding microbial adaptation to redox stresses and offers potential targets for therapeutic interventions. Further research is needed to unravel the precise mechanisms of signal transduction and the specific roles of different metalloprotein sensors in microbial metabolism.
Metalloprotein enabled redox signal transduction in microbes
- Department of Chemistry, University of Minnesota Twin Cities, USA
- Available online 11 June 2023
- Murphi T. Williams, Eaindra Yee, Grant W. Larson, Elizabeth A. Apiche, Anoop Rama Damodaran, Ambika Bhagi-Damodaran
- Current Opinion in Chemical Biology
