Achievements of the Messens lab
Functionality of peroxiredoxins
Peroxiredoxins (Prdxs), initially described as just H2O2 scavengers, have a high cellular abundance, and have now also been shown to play an important role in redox signaling. Prdxs can transfer H2O2-derived oxidative equivalents via a redox-relay to target proteins.
Peroxidatic mechanism of H2O2 sensing
Hydrogen peroxide (H₂O₂) is both a critical signaling molecule and a major contributor to oxidative stress. The prokaryotic transcription factor OxyR exemplifies a highly sensitive and specific H₂O₂ sensor: oxidation of its active-site cysteine triggers disulfide bond formation, inducing structural changes that regulate gene expression. By solving crystal structures of full-length OxyR in reduced and oxidized states, we revealed the molecular basis of its conformational flexibility. Leveraging these insights, we collaborated with the Belousov lab (Shemyakin-Ovchinnikov Institute, Moscow) to engineer HyPer7, a fluorescent H₂O₂ sensor. HyPer7 integrates OxyR with a β-barrel fluorescent protein, where H₂O₂ binding allosterically alters the chromophore environment, producing a ratiometric excitation shift. HyPer7 is bright, pH-stable, ultrafast, and ultrasensitive, enabling real-time H₂O₂ imaging.
Building on this platform, we developed HyPerFLEX (HyPer with flexible fluorogen excitation), designed for high-precision H₂O₂ monitoring in living cells. HyPerFLEX combines the redox-sensitive OxyR domain from Neisseria meningitidis with the circularly permuted fluorogenic protein Y-FAST, generating oxygen-independent fluorescence upon OxyR oxidation. This sensor offers tunable spectra from green to far-red for multicompartment imaging, even under prolonged hypoxia. HyPerFLEX surpasses HyPer7 in detecting ultralow H₂O₂ concentrations, such as during early glucose-stimulated insulin secretion, and functions in highly oxidizing environments like the ER lumen. These features make HyPerFLEX a powerful tool for studying oxidative signaling and stress responses in complex cellular contexts.
H2O2 is a messenger molecule
The plant field was also an attraction point for my research, and over the years I was increasingly more fascinated by how the H2O2 signalling induces post-translational modification of plant proteins which affected their structure, function, interaction partners, and location in the cell, sometimes with a different phenotype as a result. We quantitatively mapped the S-sulfenylated cysteines in Arabidopsis cells under H2O2 stress and thereby generated a comprehensive view on the S-sulfenylation landscape that will facilitate downstream plant redox studies.
Missing link in defence mechanism of Mycobacterium
We have discovered that Mycobacterium tuberculosis – the bacterium that causes tuberculosis – has an ingenious defence mechanism against oxygen. This knowledge is important in the search for a treatment for tuberculosis. 9.4 million people are infected with tuberculosis annually and 1.7 million people die as a result.
New Antioxidant systems
We've all read studies about the health benefits of having a life partner. The same thing is true at the molecular level, where amino acids known as cysteines are much more vulnerable to damage when single than when paired up with other cysteines. We discovered a new antioxidant systems that protects single cysteines.
Intramolecular dynamic disulfide cascade
The mechanism of pI258 arsenate reductase (ArsC) catalyzed arsenate reduction involves its P-loop structural motif and three redox active cysteines. ArsC combines a phosphatase-like nucleophilic displacement reaction with a unique intramolecular disulfide bond cascade. Within this cascade, the formation of a disulfide bond triggers a reversible ‘‘conformational switch’’ that transfers the oxidative equivalents to the surface of the protein, while releasing the reduced substrate.
Crystal clear
