A5012799478- Protein Structure and Dynamics
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- Advanced NMR Techniques and Applications
- Mass Spectrometry Techniques and Applications
- Genetic Neurodegenerative Diseases
- Molecular spectroscopy and chirality
- Bacterial Genetics and Biotechnology
- Signaling Pathways in Disease
- Bioinformatics and Genomic Networks
- Receptor Mechanisms and Signaling
- Peptidase Inhibition and Analysis
- Bacteriophages and microbial interactions
- DNA and Nucleic Acid Chemistry
- Fungal and yeast genetics research
- DNA Repair Mechanisms
- Metabolomics and Mass Spectrometry Studies
- Glycosylation and Glycoproteins Research
- Genomics and Chromatin Dynamics
- Ubiquitin and proteasome pathways
- Estrogen and related hormone effects
- Photosynthetic Processes and Mechanisms
Centre de Biologie Structurale
2016-2025
Inserm
2016-2025
Université de Montpellier
2016-2025
Centre National de la Recherche Scientifique
2016-2025
Institut de Biologie Structurale
2004-2022
Oncode Institute
2022
University Medical Center Utrecht
2022
Université Grenoble Alpes
2004-2021
Lyon College
2021
Université Claude Bernard Lyon 1
2021
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...
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...
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...
Staphylococcal immunoglobulin-binding protein, Sbi, is a 436-residue protein produced by many strains of Staphylococcus aureus. It was previously characterized as being cell surface-associated and having binding capacity for human IgG β2-glycoprotein I. Here we show using small angle x-ray scattering that the proposed extracellular region Sbi (Sbi-E) an elongated molecule consisting four globular domains, two domains (I II) novel (III IV). We further together III IV (Sbi-III-IV), well domain...
Abstract The Protein Ensemble Database (PED) (https://proteinensemble.org), which holds structural ensembles of intrinsically disordered proteins (IDPs), has been significantly updated and upgraded since its last release in 2016. new version, PED 4.0, completely redesigned reimplemented with cutting-edge technology now about six times more data (162 versus 24 entries 242 60 ensembles) a broader representation state the art ensemble generation methods than previous version. database renewed...
Abstract The Protein Ensemble Database (PED) (URL: https://proteinensemble.org) is the primary resource for depositing structural ensembles of intrinsically disordered proteins. This updated version PED reflects advancements in field, denoting a continual expansion with total 461 entries and 538 ensembles, including those generated without explicit experimental data through novel machine learning (ML) techniques. With this significant increment number few yet-unprecedented new entered...
The relation of alpha-synuclein (alphaS) aggregation to Parkinson's disease has long been recognized, but the pathogenic species and its molecular properties have yet be identified. To obtain insight into alphaS in an aggregation-prone state, we studied structural at acidic pH using NMR spectroscopy computation. demonstrated that remains natively unfolded lower pH, secondary structure propensities were changed proximity residues. ensemble conformations is characterized by a rigidification...
c-Src is a non-receptor tyrosine kinase involved in numerous signal transduction pathways. The kinase, SH3 and SH2 domains of are attached to the membrane-anchoring SH4 domain through flexible Unique domain. Here we show intra- intermolecular interactions involving suggesting presence previously unrecognized additional regulation layer c-Src. We have characterized lipid binding by domains, their intramolecular interaction its allosteric modulation SH3-binding peptide or Calcium-loaded...
Abstract Protein O -glycosylation is controlled by polypeptide GalNAc-transferases (GalNAc-Ts) that uniquely feature both a catalytic and lectin domain. The underlying molecular basis of how the domains GalNAc-Ts contribute to glycopeptide specificity catalysis remains unclear. Here we present first crystal structures complexes GalNAc-T2 with glycopeptides together enhanced sampling dynamics simulations demonstrate cooperative mechanism which domain enables free acceptor sites binding into...
The intrinsically disordered protein p15PAF regulates DNA replication and repair by binding to the proliferating cell nuclear antigen (PCNA) sliding clamp. We present structure of human p15PAF–PCNA complex. Crystallography NMR show central PCNA-interacting motif (PIP-box) tightly bound front-face PCNA. In contrast other proteins, also contacts inside of, passes through, PCNA ring. termini emerge at opposite faces ring, but remain protected from 20S proteasomal degradation. Both free...