Detection before destruction: an ultrafast laser to capture an elusive radical

Enzymes are involved in essential biological processes, but their fragility is an obstacle to obtaining their intact structures using conventional structural biology methods.

Hugo Lebrette (LMGM) and his colleagues were able to observe for the first time the atomic structure of the radical state, an extremely reactive state, of an enzyme, the mycoplasma ribonucleotide reductase, using serial crystallography coupled to an ultrafast laser.

Hugo Lebrette and his colleagues met this challenge using the concept of “diffraction before destruction”, by illuminating a stream of protein crystals with an ultrafast laser where each pulse lasts a few femtoseconds.

This result, which provides an unprecedented understanding of the structure of an enzyme, opens the way to potential therapeutic innovations.

Structure of the R2 subunit of mycoplasma ribonucleotide reductase obtained by serial femtosecond free-electron X-ray laser crystallography.Figure : Structure of the R2 subunit of mycoplasma ribonucleotide reductase obtained by serial femtosecond free-electron X-ray laser crystallography. The superposition of amino acids between the two states, radical (pink) and non-radical (grey), shows the conformational changes induced by radical acquisition.
© Martin Högbom et Hugo Lebrette

Read more :

Press release of the CNRS-Biologie :

Structure of a ribonucleotide reductase R2 protein radical. Hugo Lebrette, Vivek Srinivas, Juliane John, Oskar Aurelius, Rohit Kumar, Daniel Lundin, Aaron S Brewster, Asmit Bhowmick, Abhishek Sirohiwal, In-Sik Kim, Sheraz Gul, Cindy Pham, Kyle D Sutherlin, Philipp Simon, Agata Butryn, Pierre Aller, Allen M Orville, Franklin D Fuller, Roberto Alonso-Mori, Alexander Batyuk, Nicholas K Sauter, Vittal K Yachandra, Junko Yano, Ville R I Kaila, Britt-Marie Sjöberg, Jan Kern, Katarina Roos, Martin Högbom. Science. 2023 Oct 6;382(6666):109-113. doi: 10.1126/science.adh8160. PMID: 37797025

Contact : Hugo Lebrette

Discovery of a new component in the construction of the envelope of enterobacteria: an enhanced potential for the screening of new antibiotics

Enterobacteriaceae, Gram-negative bacilli found mainly in the intestinal flora of mammals, include species that represent a major cause of death from bacterial infection. These bacteria are surrounded by an envelope containing lipopolysaccharide that protects them from detergents and antibiotics.

The team of Raffaele Ieva (LMGM) together with collaborators from the LMGM (Yves Quentin), the IPBS (Julien Marcoux), and at the University of Warwick in UK (Robin Corey and Phillip Stansfeld), have identified a new component (called LptM) of the molecular machine that assembles lipopolysaccharide in the bacterial envelope. The researches have shown that LptM primes the machinery of lipopolysaccharide assembly by mimicking the binding of its natural substrate.

This study reveals a potential “Achilles heel” to exploit for the screening of new antimicrobial therapies.
LptM promotes oxidative maturation of the lipopolysaccharide translocon by substrate binding mimicry.

Figure : Close-up view of the lipopolysaccharide transport site in the LptD structure: biochemical assays and structural prediction show that lipoprotein LptM occupies the lipopolysaccharide transport site with its lipid tails.
© Robin Corey and Raffaele Ieva


More information :
LptM promotes oxidative maturation of the lipopolysaccharide translocon by substrate binding mimicry. Authors : Yiying Yang, Haoxiang Chen, Robin A. Corey, Violette Morales, Yves Quentin, Carine Froment, Anne Caumont-Sarcos, Cécile Albenne, Odile Burlet-Schiltz, David Ranava, Phillip J. Stansfeld, Julien Marcoux, Raffaele Ieva. Nature Communications 2023 Oct 11; 14(1):6368. doi: 10.1038/s41467-023-42007-w. PMID: 37821449


Contact : Raffaele Ieva

MicròbiOccitanie – 3rd meeting of microbiology laboratories of the Occitanie Region

The laboratories involved in microbiology research in the Occitanie Region, including the Laboratory of Microbiology and Molecular Genetics (LMGM) of the Center for Integrative Biology (CBI), are organizing the 3rd edition of the MicrobiOccitanie Symposium from July 4 to 6, 2022 at the CBI in Toulouse. On the program, conferences, round tables… Free but mandatory registration !

Reception of students at LMGM

On Friday 8th April, the LMGM-CBI welcomed two classes of 4th graders from the colleges Sainte-Marie-des-Ursulines and Saint-Louis (Toulouse). The pupils discovered the various professions of research through a presentation of the LMGM, a stakeholder of the CBI, as well as the personnel which composes it : researchers, teacher-researchers, engineers and technicians, students in master, in thesis…

Then, each student participated in “discovery” workshops: from fluorescence microscopy and image analysis to PCR (polymerase chain reaction), from protein purification to bioinformatics. These moments of exchange were very rich for all the participants.

The students loved the day !!!!