2021

Despite their life expectancy of 1 to 3 years, tardigrades are aquatic micro-animals remarkable for their ability to survive for very long periods of time under stress conditions as diverse and lethal as extreme temperatures and pressures, desiccation or even irradiation. The molecular mechanisms that confer this unique resistance to extreme conditions have remained unknown until now, despite centuries-old fascination with tardigrades. Researchers in the Protein Dynamics and Flexibility by (...)

Intrinsically disordered proteins (IDPs), i.e. proteins without stable three-dimensional structure, are extremely dynamic and it is precisely this dynamics that allows them to function and bind to different interaction partners very easily and efficiently. Rather than describing IDPs with a single structure, ensembles of many conformers have to be calculated to adequately represent their conformational landscape. In the past, nuclear magnetic resonance (NMR) spectroscopy and small angle (...)

The ’Adenovirus’ team led by Pascal Fender in the Methods & Electron Microscopy group at IBS is working on the adenovirus proteins involved in the entry of this virus, which infects many animal species and humans. This team discovered a non-infectious virus-like protein particle mimicking this virus: ADDomerTM. In 2016, in collaboration with the EMBL in Grenoble, the researchers modified this particle to expose epitopes of emerging viruses, leading to the creation of a new vaccine (...)

Andrea Dessen, team leader of the Bacterial Pathogenesis group, has been awarded the 2021 Silver Medal of the CNRS. This medal is presented to a researcher for the originality, quality, and importance of their work, which is recognized at national and international levels. Andrea Dessen is graduated with a degree in Chemical Engineering from the University of Rio de Janeiro. She did her PhD work at New York University and her postdoctoral training both at the Albert Einstein College of (...)

Hélène Malet, Associate Professor at the University of Grenoble Alpes and researcher in the Electron Microscopy and Methods group of the IBS, has been awarded the CNRS Bronze Medal for the year 2021 for her work on viral proteins involved in viral replication and transcription (details). This medal rewards the first work of a researcher, which makes him/her a talented specialist in his/her field. Viral replication and transcription are key steps of the viral cycle. Hélène Malet analyses the (...)

Bacteria adopt a morphology that is adapted to the selective pressure of their environment, which makes it an essential feature for their survival. This shape is intimately linked to the synthesis of the bacterial cell wall. In Gram + bacteria, such as Streptococcus pneumoniae, the cell wall is mainly composed of a thick layer of peptidoglycan (PG), which forms a three-dimensional network of sugars and peptides at the surface of the cell. Although the PG synthesis machineries, called (...)

Fluorescent proteins of the GFP family that change their fluorescent state upon illumination at specific wavelengths are widely used markers for super-resolution imaging modalities. The photophysical properties of these proteins, however, crucially depend on the environmental conditions in which they are expressed and used. Currently, strategies based on rational design to improve fluorescent proteins mainly exploit the mechanistic information available from X-ray crystallographic (...)

The SARS-CoV-2 spike protein is know to bind with ACE2 receptors on cell surfaces (especially in the lungs) thus allowing the entry of the virus into human cells. Scientists from the Institut Laue-Langevin (ILL), in collaboration with the Institut de Biologie Structurale (IBS), the Paul Scherrer Institut (PSI) and the Australian Nuclear Science and Technology Organisation (ANSTO), focused on the interactions between the spike protein and the rest of the cell membrane. Several model cell (...)

Pseudomonas aeruginosa can cause nosocomial infections via the ExoU toxin, which acts on plasma membrane lipids, causing their rupture and necrosis in the host cell. By discovering that ExoU requires the host DNAJC5 protein for its necrotic activity, IRIG researchers have identified the Achilles heel of this toxin. Pseudomonas aeruginosa is an opportunistic pathogenic bacterium causing nosocomial acute infections, as well as fatal chronic infections in cystic fibrosis patients. Clinical (...)

[FeFe] hydrogenases are metalloenzymes capable of catalyzing the reversible oxidation of molecular hydrogen. They use a unique organometallic center called H-aggregate, consisting of a [Fe4S4] center linked to a binuclear iron center [2Fe]H. The latter corresponds to the hydrogen binding and conversion site. The physicochemical and structural properties of this center serve as a source of inspiration for the development of catalysts for the wider use of molecular hydrogen as a renewable (...)

Broadly speaking, cells have receptors on their surface, some of which are used only for virus attachment, while others can contribute to the cellular barrier crossing. The S-glycoprotein, located on the surface of the SARS-CoV-2 Coronavirus, allows the entry of the virus into human cells via its interaction with a receptor, the ACE2 enzyme, on the surface of infected cells. IBS Scientists (M&P group), in collaboration with the CAID group and the IBS electron microscopy platform, as (...)

The peptidoglycan (PG) is an essential component of the bacterial cell wall, and plays a key role in shape maintenance and cell division. Due to the importance of PG for bacterial survival, its biosynthetic machinery has been a preferential target for antibiotic development for decades. However, little is known regarding how cell wall elongation is regulated. In this work we show that the scaffolding protein MreC from the human pathogen Pseudomonas aeruginosa plays a key role in regulation (...)

The HIV-1 envelope glycoprotein (Env) is the key target of neutralizing antibodies, blocking virus entry. Env is a metastable trimer composed of the receptor binding domain gp120 and the fusion protein subunit gp41. Upon cellular receptor binding Env undergoes a series of conformational changes notably within gp41, which pulls viral and cellular membranes into close proximity to catalyze membrane fusion and initiate infection. In this article, the EBEV group and collaborators from the (...)

Studies providing insights into adaptative process of molecules to extreme conditions are of wide fundamental interest, as evolutionary processes impact the genomic organization, shape, function and phenotype of cells and their biomolecules. Thus evolutionary biochemistry allows to understand the fundamental process of exchange between the dynamic, structural and functional properties of enzymes. In this work, scientists from the Institute of Structural Biology (IBS, Grenoble), in (...)

An international consortium* of scientists, including researchers from the IBS/DYNAMOP and IBS/SYN groups, has deciphered the mechanism and dynamics of the fatty acid photodecarboxylase (FAP) enzyme, a discovery published in Science on 08/04/2021. This photoenzyme is naturally present in many microscopic algae and uses light energy to catalyse the generation of hydrocarbons from fatty acids. To elucidate the mechanism of this unique enzyme, the research teams have combined multi-faceted (...)

Nitrogenase is a key metalloprotein that catalyzes the reduction of nitrogen to ammonia at room temperature and ambient pressure. It thus plays a major role in the global nitrogen cycle. It uses two metal centers: the P-cluster, an atypical [Fe8S7] center, which allows electron transfer to the active site itself, which is an organometallic [MoFe7S9C-(R)-homocitrate] center. Its biosynthesis requires the action of a dozen accessory proteins that constitute the NIF (for NItrogen Fixation) (...)

The 3rd French Investment Program ’EquipEx+’ aims to support new research equipment of international standard, to strengthen the excellence and competitiveness of French scientific research. Following a call for research proposals launched mid-2020, 50 proposals out of 135 were selected by an international jury end of 2020 for a total amount of 422 million euros. IBS is associated with two of the winning projects: the FranceCryoeEM project for a "National instrumentation in cryo-electron (...)

Dancing water molecules on the surface of soluble proteins provide the essential lubricant for macromolecular function. Surprisingly, polymers attached to protein surfaces have been reported to replace hydration water and bring inactive dry proteins back to life. The mechanism behind polymer-assisted functional protein motions has now been revealed by researchers from the Institut de Biologie Structurale in Grenoble, the Universities of Bordeaux, of California Irvine, of Bristol and of (...)

Bacteria possess a sophisticated arsenal of defense mechanisms that allow them to survive in adverse conditions. Adaptation to acid stress and hypoxia is crucial for the enterobacterial transmission in the gastrointestinal tract of their human host. Using three-dimensional superresolution fluorescence microscopy and electron cryo-microscopy, the researchers of the MICA group, in collaboration with the PIXEL team and the M4D platform at the IBS, have shown that in response to acid stress, (...)

We are proud to announce that Andrea Carfi, currently VP & Head of Research for Infectious Disease at Moderna, Cambridge, MA, USA, is an IBS alumnus. After receiving his doctorate under the direction of Otto Dideberg (retired) at the IBS in 1997 he completed his training as a postdoctoral fellow in Prof. Don Wiley’s group at Children’s Hospital (Harvard University) in Boston, MA, where he met the current IBS director Prof. W. Weissenhorn. Andrea Carfi then moved to industry, joining (...)