A5001250430- Protein Structure and Dynamics
- Advanced NMR Techniques and Applications
- Enzyme Structure and Function
- Molecular spectroscopy and chirality
- NMR spectroscopy and applications
- Virology and Viral Diseases
- Advanced MRI Techniques and Applications
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Electron Spin Resonance Studies
- Spectroscopy and Quantum Chemical Studies
- Photosynthetic Processes and Mechanisms
- Hemoglobin structure and function
- Mass Spectrometry Techniques and Applications
- Bacteriophages and microbial interactions
- RNA modifications and cancer
- Glycosylation and Glycoproteins Research
- Microtubule and mitosis dynamics
- HIV Research and Treatment
- Nuclear Structure and Function
- Genomics and Chromatin Dynamics
- Respiratory viral infections research
- Bacterial Genetics and Biotechnology
- Influenza Virus Research Studies
- Alzheimer's disease research and treatments
Centre National de la Recherche Scientifique
2016-2025
Université Grenoble Alpes
2016-2025
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2016-2025
Institut de Biologie Structurale
2016-2025
Centre National pour la Recherche Scientifique et Technique (CNRST)
2025
CEA Grenoble
2015-2024
Université Paris-Saclay
2018
Université Paris-Sud
2018
Université Joseph Fourier
2006-2015
University of Oxford
1985-2015
Structural analysis of flexible macromolecular systems such as intrinsically disordered or multidomain proteins with linkers is a difficult task high-resolution techniques are barely applicable. A new approach, ensemble optimization method (EOM), proposed to quantitatively characterize in solution using small-angle X-ray scattering (SAXS). The flexibility taken into account by allowing for the coexistence different conformations protein contributing experimental pattern. These conformers...
Natively unfolded proteins play key roles in normal and pathological biochemical processes. Despite their importance for function, this category of remains beyond the reach classical structural biology because inherent conformational heterogeneity. We present a description intrinsic sampling based on residue-specific φ/Ψ propensities from loop regions folded protein database simple volume exclusion. This approach is used to propose model 57-aa, natively disordered region nucleocapsid-binding...
Proteins with intrinsically disordered domains are implicated in a vast range of biological processes, especially cell signaling and regulation. Having solved the quaternary structure folded tumor suppressor p53 by multidisciplinary approach, we have now determined average ensemble N-terminal transactivation domain (TAD) using residual dipolar couplings (RDCs) from NMR spectroscopy small-angle x-ray scattering (SAXS). Remarkably, not only were able to measure RDCs isolated TAD, but also do...
Abstract Motivation: Intrinsically disordered proteins (IDPs) represent a significant fraction of the human proteome. The classical structure function paradigm that has successfully underpinned our understanding molecular biology breaks down when considering have no stable tertiary in their functional form. One convenient approach is to describe protein terms an equilibrium rapidly inter-converting conformers. Currently, tools generate such ensemble descriptions are extremely rare, and...
Intrinsically disordered proteins (IDPs) are predicted to represent a significant fraction of the human genome, and development meaningful molecular descriptions these remains key challenge for contemporary structural biology. In order describe conformational behavior IDPs, representation state based on diverse sources data that often exhibit complex very different averaging is required. this study, we propose combination paramagnetic relaxation enhancements (PREs) residual dipolar couplings...
The mechanisms by which intrinsically disordered proteins engage in rapid and highly selective binding is a subject of considerable interest represents central paradigm to nuclear pore complex (NPC) function, where transport receptors (NTRs) move through the NPC phenylalanine-glycine-rich nucleoporins (FG-Nups). Combining single-molecule fluorescence, molecular simulations, magnetic resonance, we show that rapidly fluctuating FG-Nup populates an ensemble conformations are prone bind NTRs...
A hierarchy of protein motions Functioning proteins are not static but explore complex conformational energy landscapes. Lewandowski et al. used multinuclear solid-state nuclear magnetic resonance experiments to measure motion over a broad range temperatures and time scales. Above 160 K there was strong coupling between solvent motion. The as the temperature increased revealed dynamic modes that relate solvent, sidechain, backbone Science , this issue p. 578
The goal of pE-DB (http://pedb.vib.be) is to serve as an openly accessible database for the deposition structural ensembles intrinsically disordered proteins (IDPs) and denatured based on nuclear magnetic resonance spectroscopy, small-angle X-ray scattering other data measured in solution. Owing inherent flexibility IDPs, solution techniques are particularly appropriate characterizing their biophysical properties, agreement with these provide a convenient tool describing underlying...
Measles virus proteins form liquid droplets where they can encapsidate their genomic material.
The processes of genome replication and transcription SARS-CoV-2 represent important targets for viral inhibition. Betacoronaviral nucleoprotein (N) is a highly dynamic cofactor the replication-transcription complex (RTC), whose function depends on an essential interaction with amino-terminal ubiquitin-like domain nsp3 (Ubl1). Here, we describe this (dissociation constant - 30 to 200 nM) at atomic resolution. implicates two linear motifs in intrinsically disordered linker (N3), hydrophobic...
Liquid–liquid phase separation of flexible biomolecules has been identified as a ubiquitous phenomenon underlying the formation membraneless organelles that harbor multitude essential cellular processes. We use nuclear magnetic resonance (NMR) spectroscopy to compare dynamic properties an intrinsically disordered protein (measles virus NTAIL) in dilute and dense phases at atomic resolution. By measuring 15N NMR relaxation different field strengths, we are able characterize dynamics crowded...
Despite their importance for biological activity, slower molecular motions beyond the nanosecond range remain poorly understood. We have assembled an unprecedented set of experimental NMR data, comprising up to 27 residual dipolar couplings per amino acid, define nature and amplitude backbone motion in protein G using Gaussian axial fluctuation model three dimensions. Slower occur loops, beta-sheet, are absent other regions molecule, including alpha-helix. In beta-sheet alternating pattern...
Intrinsically unstructured proteins play key biochemical roles in a vast range of normal and pathological processes. To study these systems, it is necessary to invoke an ensemble rapidly interconverting conformations. Residual dipolar couplings (RDCs) are particularly powerful probes the behavior unfolded proteins, reporting on time ensemble-averaged conformations up beyond millisecond scale. In this study, we present novel interpretation RDCs systems that simultaneously defines long-range...
Tau, a natively unstructured protein that regulates the organization of neuronal microtubules, is also found in high concentrations neurofibrillary tangles Alzheimer's disease and other neurodegenerative disorders. The conformational transition between these vastly different healthy pathological forms remains poorly understood. We have measured residual dipolar couplings (RDCs), J-couplings, nuclear Overhauser enhancement (NOE) construct K18 tau, containing all four repeat domains R1-R4. NHN...
Tau is one of the two main proteins involved in pathology Alzheimer's disease via formation β-sheet rich intracellular aggregates named paired helical filaments (PHFs). Given that tau a natively unfolded protein with no folded core (even upon binding to physiological partners such as microtubules), its structural analysis by high-resolution techniques has been difficult. In this study, employing solution small-angle X-ray scattering from full length isoforms and variety deletion point...
An atomic resolution characterization of the structural properties unfolded proteins that explicitly invokes highly dynamic nature state will be extremely important for development a quantitative understanding thermodynamic basis protein folding and stability. Here we develop novel approach using residual dipolar couplings (RDCs) from to determine conformational behavior on an amino acid specific basis. Conformational sampling is described in terms ensembles structures selected large pool...