Institut de Biologie StructuraleGrenoble / France


SARS-CoV-2 : discovery of a new mode of transmission

Glycoprotein S, located on the SARS-CoV-2 virus membrane, is known to allow the entry of this virus into human cells via the ACE2 receptor, present on the surface of infected cells. The Membrane & Pathogens group, in collaboration with IBS/IRPAS and MEM groups and groups from Spain and Italy, have discovered that C-type lectin receptors (CLRS) of antigen-presenting cells are involved in the overall infection process. DC-SIGN, L-SIGN, Langerin and MGL bind to diverse glycans of the spike using multiple interaction areas. After attaching the virus to the cell, these lectin receptors are capable of promoting virus transfer to permissive ACE2+ cells. It is therefore a new mode of transmission in the infection process, detailed in an article posted on the BioRxiv preprint site ( which is currently under evaluation by a peer-reviewed journal. They have also shown that it is possible to inhibit this new mode of virus transmission through the use of glycomimetics (sugar mimetics created by organic synthesis) previously developed at IBS.

DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist. Thépaut M, Luczkowiak J, Vivès C, Labiod N, Bally I, Lasala F, Grimoire Y, Fenel D, Sattin S, Thielens N, Schoehn G, Bernardi A, Delgado R, Fieschi F. doi :

Contact : Franck Fieschi, UGA professor attached to the IBS (Membrane & Pathogens group)

Cryo-EM structure of a key enzyme in action gives insights into the replication of a human pathogenic virus

Bunyavirales is an order of segmented negative-strand RNA viruses comprising several life-threatening human pathogens for which there is currently no treatment (La Crosse virus, Hantaan virus, Crimean Congo virus, Lassa virus). The replication and transcription of their genome are essential steps of their viral cycle and are catalyzed by a key viral enzyme : the RNA-dependent RNA polymerase. The MEM group at IBS, in collaboration with Dr. Cusack’s group at EMBL Grenoble, describes here the structure of the complete RNA-polymerase of the La Crosse virus obtained at 3 Å resolution by cryo electron microscopy, using data collected on the Glacios cryo-microscopes from IBS and Krios from ESRF. This structure reveals the position and organization of the C-terminal part of the RNA polymerase which includes a cap-binding domain necessary for transcription initiation. Two states could be visualized, pre-initiation and elongation. In particular, this allows to highlight the conformational changes necessary for the formation of a double-stranded 10-base pair RNA in the active site cavity during elongation. The structural details and dynamics of the functional elements identified provide mechanistic insight into bunyavirus transcription and may be crucial for the future development of RNA polymerase inhibitors.

Pre-initiation and elongation structures of full-length La Crosse virus polymerase reveal functionally important conformational change. Benoît Arragain, Grégory Effantin, Piotr Gerlach , Juan Reguera , Guy Schoehn, Stephen Cusack, Hélène Malet. Nature Communications 2020 ;11(1):3590. doi : 10.1038/s41467-020-17349-4.

Contact : Hélène Malet

Following protein aggregation in real time by neutron spectroscopy

Protein aggregation into amyloid superstructures is the molecular manifestation of a large variety of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Evidence is increasing that transient on-pathway oligomers are actually the toxic species, such that time-resolved monitoring of protein aggregation is highly desirable. Whereas time-resolved structural techniques have been developed and applied to study protein aggregation, methods accessing protein center-of-mass and internal diffusion dynamics remain only sparsely available. Yet, changes in protein dynamics have been postulated to play an essential role in driving and accompanying protein aggregation.
Scientists of the Institut Laue Langevin, the Institut de Biologie Structurale and the University of Copenhagen developed a time-resolved version of incoherent neutron scattering experiments on IN16B to follow protein aggregation and applied it to study the assembly of lysozyme in aqueous solution into particulate superstructures. Surprisingly, the internal protein dynamics on the nano-to picosecond time scale does not change during the entire aggregation process. The center-of-mass diffusion, on the other hand, decreases as aggregation proceeds and can be well explained by a single exponential process. By complementing the neutron results with fluorescence measurements, electron microscopy, infrared spectroscopy, x-ray powder diffraction, and dynamic light scattering, a comprehensive picture was painted in which lysozyme particulate formation is a one-step process with protein backbone and side chain dynamics remaining unchanged throughout aggregation.
The work establishes a framework to follow protein aggregation quantitatively in real time at a molecular level, simultaneously accessing center-of-mass and internal diffusivities, which will be invaluable for addressing pathological pathways of protein aggregation. This framework is not limited to proteins, but can be applied to macromolecules in general to study a large variety of processes such as self-assembly and emerging aggregates and crystals.

Tracking Internal and Global Diffusive Dynamics During Protein Aggregation by High-Resolution Neutron Spectroscopy. Pounot K, Chaaban H, Foderà V, Schirò G, Weik M, Seydel T. J.Phys.Chem.Lett. 11, 15 (2020)

Contact : Martin Weik