2018

Combining X-ray crystallography, EPR spectroscopy and theoretical calculations, researchers from IBS-METALLO and INAC-CAMPS have determined the fine mechanism for carboxyl radical migration during methylindolic acid biosynthesis. A preorganized active site and restrained motions are essential to afford an efficient reaction. Radical S-Adenosyl-l-methionine Tryptophan Lyase (NosL): How the Protein Controls the Carboxyl Radical •CO2- Migration. Amara P, Mouesca JM, Bella M, Martin L, (…)

By closely studying CCR5, one of the entry points of HIV into cells, researchers from Inserm, the Institut Pasteur, the University of Toulouse III - Paul Sabatier, the CNRS and IBS, demonstrate that its morphology determines the propensity of the virus to infect the body. This work supported by the ANRS and published in the Plos Pathogens journal is a new step towards understanding the role of CCR5 in HIV infection and as a target for blocking the entry of the virus into cells (details). (…)

Nanodiamonds (NDs) have many potential biomedical applications, such as cancer therapy, deep brain stimulation, and dentistry. In collaboration with the Service de Chimie Bioorganique et de Marquage (SCBM, CEA, Université Paris-Saclay), IBS researchers have shown that, even though C1q does not trigger the immune complement system cascade, its interaction modifies phagocytosis and cytokine response to NDs and may interfere with the multiple physiological and pathological processes that (…)

Our genetic information is encoded by DNA, which is packaged in the cell nucleus in the form of chromatin. The basic building block of chromatin is the nucleosome, formed by the wrapping of DNA around a core of basic proteins called histones. Nucleosomes pack together to form a nucleosomal array, whose structure is highly dynamic and whose conformation plays a key role in gene expression. Notably, the formation of a compact 30-nm fiber is associated with the inactivation of gene expression. (…)

Mitochondria synthesize the adenosine triphosphate (ATP) molecule, which is able to transport chemical energy within cells. The amount of ATP transported daily through the mitochondrial membranes to supply our cells corresponds approximately to our body weight. This transport of mitochondrial ATP is carried out by membrane proteins, produced themselves outside the mitochondria, and which have to be inserted into the membrane where they « work ». Because these membrane proteins are insoluble (…)

Cécile Morlot (IBS/Pneumococcus group) is the recipient of a bronze medal of the CNRS 2018. This distinction rewards an on-going and fruitful research activity, which makes him/her a specialist with talent within a particular research field. During her thesis at the Institute for Structural Biology (IBS) in the group of Thierry Vernet, Cécile developed a fluorescent labelling method to localize, using optical microscopy, proteins in charge of cell division in an important human pathogen: (…)

This result, published in Nature, describes the activation cycle of the 5-HT3 receptor, belonging to the family of serotonin receptors. These receptors influence various biological and neurological processes such as anxiety, appetite, mood and nausea. 5-HT3 receptors are the main target of anti-emetic drugs widely used to alleviate the side effect of chemotherapies. Scientists from the IBS, the Institut Pasteur, the University of Lorraine, the University of Copenhagen, Danemark, the (…)

The universality of peptidoglycan in bacteria underlies the broad spectrum of many successful antibiotics. However, in our times of widespread resistance, the diversity of peptidoglycan modifications offers a variety of new antibacterials targets. In some Gram-positive species such as Streptococcus pneumoniae, Staphylococcus aureus, or Mycobacterium tuberculosis, the second residue of the peptidoglycan precursor, D-glutamate, is amidated into iso-D-glutamine by the essential amidotransferase (…)

Many fundamental cellular functions are performed by large protein assemblies. This applies in particular to protein quality control, the process by which cells ensure the recycling or correct folding of their main constituents, in order to avoid the accumulation of poorly folded proteins, aggregates or fibrils. These large machineries - chaperones, proteases and peptidases - are complex and dynamic. The studies of such biological machines present a significant challenge, due to the very (…)

Current hypotheses about the origin of life posit that it may have started with either the replication, in a primordial soup, of genetic information-containing polymers with limited catalytic properties, (the “RNA World”), or with autocatalytic, and possibly interacting, metabolic pathways taking place on, or near, mineral surfaces. The latter possibility can be explored if a continuous geochemical, catalytically dynamic process is assumed. In this Essay it is speculated that the synthesis (…)

The European Research Council (ERC) has awarded a "Starting Grant" to Sigrid Milles, ‘flexibility and dynamics of proteins’ group at the IBS, to study intrinsically disordered proteins in endocytosis by single molecule fluorescence and nuclear magnetic resonance spectroscopy. Sigrid Milles is a CNRS researcher at the Institut de Biologie Structurale. Her project, named ‘MultiMotif’, has been selected for funding through an ERC Starting Grant over the next five years. Scientific excellence (…)

X-ray free-electron lasers (XFELs) are novel X-ray sources that provide femtosecond pulses of a peak brilliance that exceeds that of synchrotron sources by nine orders of magnitude. The short duration of the pulses matches the chemical time scale of femtoseconds, allowing the investigation of the dynamics of matter in a time-resolved manner and enables the analysis of highly radiation-sensitive objects. IBS researchers participated in one of the first experiments at the newly built European (…)

IBS Researchers, in collaboration with the CIRI, discovered a novel interaction between two proteins from the measles virus. This ultra-weak interaction, involving only four amino acids situated in a very flexible and dynamic protein region, is essential for measles virus replication. This newly discovered interaction constitutes a new target to treat measles infection, but also infection by other viruses from the same family, that comprises highly dangerous human pathogens. These results (…)

Hydrogenases are enzymes of considerable interest for their potential biotechnological applications both as catalysts in biofuel cells and hydrogen producers. However, these applications can be greatly affected by their reactions with atmospheric oxygen. In order to better understand this problem, we have investigated a single mutation of the naturally O2-tolerant E. coli [NiFe] hydrogenase-1, which makes it O2-sensitive by changing its [4Fe-3S] cluster into a novel [4Fe-4S] cluster. Our (…)

Complement receptor type 1 (CR1) is a multi modular membrane receptor involved in the clearance of complement opsonized components from the blood stream. By binding targets tagged with complement-opsonins, the CR1 receptor on the surface of erythrocytes contributes to their elimination by transport to the liver, then phagocytosis by monocytes, macrophages or neutrophils. CR1 is composed of 30 homologous complement control protein (CCP) modules and is a receptor for complement-opsonins C3b (…)

Many cellular processes involve membrane proteins (MPs) and characterization of their structure, interactions and dynamics remains a challenge for structural biology. The difficulty is related to the need to extract these proteins from their biological membrane in order to study them. Detergents are frequently used but their physical properties differ from those of lipids and could alter the structural organization of MPs. In this study, a family of membrane proteins, mitochondrial (…)

Mevalonate is a starting material to synthesize many chemicals in industry; it is also the building block of the lipids from all archaea. Scientists at the IBS and and collaborators at the Max Planck Institute for Terrestrial Microbiology in Marburg and ENS Lyon discovered a coupling between the two enzymes responsible for the first step in mevalonate biosynthesis in archaea. This finding explain how archaea can produce mevalonate at high rate to support their growth, and can be applied in (…)

Intrinsically Disordered Proteins (IPDs) are functionally active despite lacking a well-defined three-dimensional structure. Their great flexibility allows them to easily adapt to the surface of their partners and they are able to fold during interaction. In some cases, they may even form a so-called fuzzy complex, in which the IPD does not adopt a single conformation defined on the partner’s surface, but continues to sample multiple conformations in a highly dynamic complex. The FDP group (…)

Green fluorescent proteins (GFPs) are genetically encoded markers allowing the localization of down to individual proteins by optical microscopy. Their fluorophore is formed from three amino acids and is located at the center of a beta barrel that protects it from the environment. GFPs have high absorption coefficient and fluorescence yield, but only moderate photostability. They can reversibly form temporary nonfluorescent “dark” states before definitely losing fluorescence after about (…)

Biofilms are bacterial communities with high antibiotic resistance. Within biofilms, bacteria exchange information chemically - a mechanism called quorum-sensing. Researchers at the Institute de Biologie Structurale in Grenoble, the University of the Mediterranean in Marseille and the Jacobs University in Bremen have shown that the gram-negative pathogen Providencia stuartii forms floating communities within which adjacent cells are in apparent contact,before depositing as canonical (…)