2024

Enzymes are responsible for the chemical reactions that provide energy and transform various constituents during cellular metabolism. How they acquired their specific functions during evolution is a fundamental question. Indeed, the way they function today has evolved over very long periods of time. In collaboration with LBBE Lyon and LPC Orsay, researchers from the Extremophiles and Large Molecular Assemblies Group of the IBS have characterized very ancient enzymes, from extremophiles (…)

DC-SIGN and L-SIGN are two C-type lectin receptors (CLRs) used by SARS-CoV-2 as viral co-receptors. SARS-CoV-2 manipulates both DC-SIGN and L-SIGN to enhance infection, raising interest in developing antagonists for these receptors. These two receptors, very similar (82% identity), have different localizations. DC-SIGN, found in dendritic cells, shapes the immune response by recognizing carbohydrate patterns on pathogens. In contrast, L-SIGN is expressed in endothelial cells of the (…)

Cryo-electron microscopy (cryo-EM) is a powerful technique for structural biology, but obtaining optimal grids for data collection is challenging. Cryo-EM samples are vitrified in their native solution on grids with a holey carbon support film. Protein molecules in vitreous ice suspended in the holes of the support film are then imaged. The ice layer must be thick enough to preserve the protein structure and thin enough to obtain the best signal-to-noise ratio. Controlling ice thickness is (…)

This Titan Krios transmission electron microscope, funded by the french program ’Investissement d’Avenir 3’, is specially designed for cryo-electron microscopy (cryoEM) in biology. Hosted by ESRF, it is made available to the French and European scientific community and operated by the IBS and the ISBG. Details below. This state-of-the-art instrument is part of a network of three microscopes located in France, at the IGBMC in Illkirch-Graffenstaden, the Synchrotron Soleil in Saint-Aubin, (…)

Every year, the French Academy of Sciences awards numerous prizes and medals, covering fundamental and applied science in wide range of fields. IBS is proud to count one of its researchers among the 2024 laureates. Indeed the Dr and Mrs Henri Labbé Prize by the French Academy of Sciences was awarded to Yvain Nicolet, group leader of the Metalloprotein group at the Institut de Biologie Structurale (IBS/METALLO). Yvain Nicolet investigates the structure-function relationships of (…)

Radical SAM enzymes (rSAM) and oxygenases are two of the most common and versatile metalloprotein structural domains in nature. In collaboration with groups from Singapore and China, we have identified a group of fused rSAM-oxygenase enzymes that catalyze crosslink formation and OH addition in ribosomally synthesized and translationally modified peptides (RiPPs). Crystal structure determination of the oxygenase domain, revealed a novel structural fold, named $\alpha$KG-HExxH, different to (…)

The mitogen-activated protein kinases (MAPKs) are vital components of eukaryotic signal transduction networks, ensuring appropriate cellularresponses to diverse extracellular stimuli. Among the three major MAPK pathways, the c-Jun N-terminal kinase (JNK) cascade is essential for regulating stress responses and apoptosis. The homologous scaffold proteins JIP1 and JIP2 play a critical role in the JNK signalling pathway by assembling multiple kinases to enhance the efficiency and specificity of (…)

Nucleoid remodeling is a common stress response strategy in bacteria to protect their genetic material. This process is regulated by small proteins, known as NAPs or Nucleoid-Associated Proteins, which interact with DNA and play a key role in the organisation and regulation of the bacterial genome. Using advanced conventional and single-molecule localization microscopy approaches, the I2SR group, in collaboration with F. Confalonieri’s team at I2BC, recently demonstrated that exposure to (…)

The nucleocapsid protein (N) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encapsidates the viral genome and is essential for the replication of this important human pathogen. The central region of the protein is highly disordered, and is found to be hyperphosphorylated in infected cells, a modification that changes the function of the protein during the viral cycle. Remarkably the protein is not phosphorylated in the infectious particle (the virion). Researchers at the (…)

Bunyaviricetes is a large class of viruses that have a segmented negative stranded RNA genome. Divided into 15 families, this class contains major human pathogens, such as Lassa or Crimean Congo Hemorrhagic fever viruses that are considered as priority viruses by the World Health Organization due to their pathogenicity and the lack of available countermeasures. Other viruses of the Bunyaviricetes class are emerging, such as Hantaan virus, that causes hemorrhagic fever in humans, with 15% (…)

The 2024 Ivano Bertini Award was awarded to Martin Blackledge, head of the Protein Dynamics and Flexibility by NMR Group of the IBS (IBS/FDP). This prize, offered by Instruct, recognises a significant achievement in frontier research that utilises an integrative structural biology approach. In particular, it rewards his pioneering work on intrinsically-disordered proteins using NMR. To know more

NADPH oxidases (NOX) are transmembrane proteins, widely spread in eukaryotes and prokaryotes, that produce reactive oxygen species (ROS). Eukaryotes use the ROS products for innate immune defence and signaling in critical (patho)physiological processes. These enzymes facilitate electron transfer through membrane from NAD(P)H to O2 via internal relays involving a flavin cofactor (FAD) and heme groups. The production of ROS, due to their potential toxicity, implies a tight regulation of these (…)

Proteoglycans are proteins associated with polysaccharide chains known as glycosaminoglycans (GAGs), with heparan sulfates (HS) and chondroitin sulfates (CS) being the most representative. The chain synthesis is carried out by glycosyltransferases in the Golgi apparatus and begins with the formation of a tetrasaccharide composed of a xylose, two galactoses, and a glucuronic acid. The decision-making step occurs during the addition of the fifth sugar: the transfer of a GlcNAc residue by the (…)

Polymixins (such as polymixin B (PMB) or colistin) are among the drugs used as a last resort for multi-resistant Pseudomonas aeruginosa, a major human opportunistic pathogen. The IBS/PBRC group in collaboration with teams from the Besançon hospital and the CEA Grenoble (EDyP, IRIG), revealed a new strategy used by certain strains of P. aeruginosa to sense and trigger a complex response following PMB treatment. Using clinical strains and combining microbiology, proteomics and 3D structure (…)

Bacterial spores are dormant cells that can resist to multiple stresses, including antibiotics, disinfectants, irradiation and high temperatures. Such resilience proves advantageous when spores are used for human benefit, as in probiotics, but it poses a major problem for public health, food safety or biowarfare when it comes to spores of pathogenic bacteria. The spore owes its toughness to durable intracellular and extracellular assemblies that protect the cell and its genetic material, (…)

Channelrhodopsins are light-activated ion channels found in microbes. Although their roles often remain enigmatic, they are widely used in optogenetics to photocontrol specific neurons in higher organisms. Widely distributed in microorganisms, they are also encoded in the genomes of giant viruses infecting phytoplankton, where their function is not established. The Channels team of the Membrane Transporters Group (IBS/MEMBRANE) examined the properties of viral channelrhodopsins type 1 (…)