2019

Scientists estimate that one third of human proteins are intrinsically disordered proteins (IDPs), i.e. proteins without a stable three-dimensional structure. Very flexible, these biomolcules can adapt to several physiological partners and adopt a multitude of conformations. Their functioning remains poorly understood even though they play essential roles in all living organisms. Nuclear magnetic resonance (NMR) spectroscopy is ideally suited to the investigation of this behavior at atomic (...)

The key to HIV vaccine development is the induction of broadly neutralizing antibodies (bnAb). The currently known bnAbs are directed against six regions of the HIV envelope glycoprotein trimer composed of gp120 and gp41. Several bnAbs that target a highly conserved epitope named "MPER" located on gp41 have been identified. Candidates for the development of a vaccine based on peptides mimicking this epitope have been tested without success. What is the reason for these failures? In this (...)

On the 30st of Octobre 2019, Sigrid Milles received the Paoletti Prize 2019 for her work on intrinsically disordered proteins studied by single molecule fluorescence and nuclear magnetic resonance spectroscopy. This prestigious award is presented in memory of Claude Paoletti, former chief scientist of the CNRS Life Sciences Department who took many initiatives to support young (...)

Thursday 03 October saw the official opening of the 2019 Science Festival on the EPN Campus. The launching of the 2019 Science Festival in Isere began with visits of the NMR and electron microscopy platforms of the IBS, the ESRF tunnel, the EMBL-IBS partnership platform for high throughput protein crystallography, the Science building and two ILL-ESRF joint laboratories were proposed. Then the opening ceremony in the IBS seminar room was attended by Chloé Lombard, representing Mr Préfet (...)

Infectious diseases continue to decimate populations around the world. Among the means at our disposal to counter these threats, vaccination has proven to be exceptionally powerful. Smallpox has been eradicated, measles and polio are controlled by vaccination. However, serious threats still exist, as evidenced by epidemics caused by the Ebola or Zika viruses. Another recent example is the Chikungunya virus, a viral pathogen transmitted by the bite of a tiger mosquito. Once confined to (...)

Given their complexity, the structure determination of high molecular weight biological machinery often remains a challenge for experimental methods available to structuralists. Researchers from the MEM, NMR and DYNAMOP groups at IBS, in collaboration with the University of Frankfurt and the NIH, have developed an integrated structure determination approach that simultaneously uses NMR and EM data to overcome the limits of each of these methods. The approach enables structure determination (...)

Aromatic residues play key roles in many proteins, and are involved in protein-ligand and protein-protein interactions. They also can be found in the hydrophobic core of proteins, where they are crucial for protein stability. For these reasons, studying their dynamics can provide rich information on reaction mechanisms and folding. Although solution-state NMR has been used to study the motions of aromatic residues for decades, these studies have been limited to small proteins, due to (...)

The finding that an inhibitor activates an enzyme appears counterintuitive. How can an inhibitor, which binds to the active site, increase the enzyme’s activity? In this study, researchers at IBS (NMR, MICA and PG groups), in collaboration with colleagues in Nancy and Zaragoza, revealed how the 300 kDa large protease ClpP undergoes this intriguing allosteric activation by an inhibitor as well as by substrates. A multi-technique approach, involving X-ray crystallography, solution- and (...)

In this study, IBS researchers (VIC group/Timmins team in collaboration with DYNAMOP group/ Bourgeois team) demonstrated through conventional fluorescence microscopy and super-resolution approaches, the organization and dynamics of the nucleoid of Deinococcus radiodurans, a bacterium well known for its outstanding radiation resistance. This work revealed for the first time that bacterial nucleoids are complex entities that change structure as a function of the cell cycle and can adopt more (...)

The virus Hantaan, that belongs to the Hantaviridae family (Bunyavirales order) and is transmitted by rats and mice, can give rise in human to fatal hemorrhagic fevers against which no treatment is currently available. The genomic segments of this negative strand RNA virus are surrounded by multiple copies of nucleoproteins that together form helical nucleocapsids. The Methods and Electron Microscopy Group used state-of-the art cryo-electron microscopy to determine the 3.3 Å resolution (...)

There are several cellular mechanisms to fight cancer. One of the major actors is the p53 protein which, when it becomes inactive, greatly increases the risk of cancer development. Maternally expressed 3 (MEG3), a long non-coding RNA (lncRNA, >500 kDa), is another molecule that prevents cancer through its stimulating activity on p53. The results of a study on the structure of MEG3, published in Molecular Cell, could help to advance the diagnosis and treatment of certain types of cancer. It (...)

Super-resolution microscopy makes it possible to observe living matter at the nanoscopic scale, not only from a structural point of view but also from a dynamic point of view. In the latter case, individual target molecules are monitored as they diffuse into a cell: this is the "sptPALM" technique (single-particle-tracking localization microscopy). However, a major obstacle to this technique is the imperfection of the fluorescent markers used to label the target molecules. These markers are (...)

Bacteria have developed different secretion systems that allow them to secrete toxins to the outside of the cell. These machines are important for infection, colonization and microbial communication processes. An important element of many of these machines is secretin, a membrane protein that forms a pore on the bacterial surface allowing toxins to escape. Using cryo electron microscopy, crystallography, and microbial genetics techniques, the MEM and PATBAC groups of IBS, in collaboration (...)

Heparan sulfate (HS) are sulfated polysaccharides of the Glycosaminoglycans family that participate in many cellular processes because of their ability to interact and modulate a wide range of signalling proteins. These interactions involve particular HS motifs, defined by their saccharide sequence and sulfation profile. However, the structural features of these functional domains remain mostly unknown, due to the molecular complexity of these polysaccharides and a lack of tools dedicated (...)

New therapeutic strategies targeting influenza are actively sought due to limitations in current drugs available. Host-directed therapy is an emerging concept to target host functions involved in pathogen life cycles and/or pathogenesis, rather than pathogen components themselves. From this perspective, researchers from the IBS/VRM group, in collaboration with the Institut Pasteur, University Paris Diderot and University Paris Descartes, focused on an essential host partner of influenza (...)

Many cellular processes such as endosomal vesicle budding, virus budding, and cytokinesis require extensive membrane remodeling by the endosomal sorting complex required for transport III (ESCRT-III). ESCRT-III protein family members form spirals with variable diameters in vitro and in vivo inside tubular membrane structures, which need to be constricted to proceed to membrane fission. Here, researchers of the group ’Entry and Budding of Enveloped Viruses’, in collaboration with the (...)

The European Research Council (ERC) has awarded an "Advanced Grant" to Martin Blackledge, group leader of the Institut de Biologie Structurale (IBS - CEA/CNRS/UGA mixed research unit), for his project on the atomic resolution description of highly dynamic molecular assemblies and their role in viral replication. Martin Blackledge is FDP group leader and Deputy Director at the IBS in Grenoble. His project entitled "DynamicAssemblies" will receive € 2.5 million financial support from the ERC (...)

Measles virus is a highly contagious human pathogen that is experiencing a dangerous resurgence throughout the world, including Europe. Replication of the virus requires encapsidation of the RNA viral genome by the viral nucleoprotein, assembling into molecular suprastructures called nucleocapsids. Researchers at the IBS have developed experimental methods (1) to encapsidate specific RNA sequences in vitro, allowing the high resolution (3.3Å) three dimensional structure determination of (...)

Photosymbiosis between single-celled hosts and microalgae is common in oceanic plankton. However, the functioning of this ecologically important cell-cell interaction and the subcellular mechanisms allowing the host to accommodate and benefit from its microalgae remain enigmatic. Here, using a combination of quantitative single-cell structural and chemical imaging techniques, a collaboration of researchers show that the structural organization, physiology, and trophic status of the algal (...)

Heparan sulfate belongs to the family of glycosaminoglycans, a group of negatively charged polysaccharides, present in large quantities on cell surfaces and in interstitial tissues. They exert their activities by interacting with a large number of proteins, controlling their mechanism of action and thus intervening in most of the major biological functions (morphogenesis, division, signalling and cell migration, inflammation and immune responses, angiogenesis and tissue repair,… etc.) as (...)