A5073259471- Advanced Electron Microscopy Techniques and Applications
- Electron and X-Ray Spectroscopy Techniques
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Photosynthetic Processes and Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Protein Structure and Dynamics
- Nanopore and Nanochannel Transport Studies
- Computational Drug Discovery Methods
- Fault Detection and Control Systems
- Parallel Computing and Optimization Techniques
- Real-time simulation and control systems
- HER2/EGFR in Cancer Research
- ATP Synthase and ATPases Research
- Endoplasmic Reticulum Stress and Disease
- Data Visualization and Analytics
- thermodynamics and calorimetric analyses
- Peptidase Inhibition and Analysis
- Genomics and Phylogenetic Studies
- Force Microscopy Techniques and Applications
- Innovative Human-Technology Interaction
- Genetics, Bioinformatics, and Biomedical Research
- Toxin Mechanisms and Immunotoxins
- Lipid Membrane Structure and Behavior
- Galectins and Cancer Biology
Institut de minéralogie, de physique des matériaux et de cosmochimie
2021-2024
Sorbonne Université
2022-2024
Centre National de la Recherche Scientifique
2021-2024
The University of Melbourne
2022-2024
Université Grenoble Alpes
2024
Institut polytechnique de Grenoble
2024
Laboratoire Jean Kuntzmann
2024
Structure et Instabilité des Génomes
2023
Sorbonne University Abu Dhabi
2023
Génomique Bioinformatique et Applications
2022
Alpha-actinin is a crucial actin-binding protein involved in cellular functions like muscle contractility, mechanosensation, and cell division. Studying its atomic structure dynamics challenging due to complexity imaging limitations. To address this, we developed SimHS-AFMfit, integrating high-speed AFM (HS-AFM), AFMfit (a flexible fitting technique), molecular (MD) simulations. This approach successfully converted 2D images into 3D conformations, revealing the conformational of Ca2+-bound...
The AAA + ATPase p97 is an essential unfoldase/segragase involved in a multitude of cellular processes. It functions as molecular machine critical for protein homeostasis, homotypic membrane fusion events and organelle biogenesis during mitosis which it acts concert with cofactors p47 p37. Cofactors assist extracting unfolding substrates through ATP hydrolysis. In contrast to other p97's cofactors, p37 uniquely increases the activity p97. Disease-causing mutations p97, including that cause...
Cryo electron tomography (cryo-ET) allows observing macromolecular complexes in their native environment. The common routine of subtomogram averaging (STA) obtaining the three-dimensional (3D) structure abundant complexes, and can be coupled with discrete classification to reveal conformational heterogeneity sample. However, number extracted from cryo-ET data is usually small, which restricts discrete-classification results a small enough populated states and, thus, largely incomplete...
Understanding how structure and function meet to drive biological processes is progressively shifting the cryoEM field towards a more advanced analysis of macromolecular flexibility. Thanks techniques such as single-particle electron tomography, it possible image macromolecule in different states, information that can subsequently be extracted through image-processing methods build richer approximation conformational landscape. However, interoperability all these algorithms remains...
Abstract Atomic Force Microscopy (AFM) offers a unique opportunity to study the conformational dynamics of proteins in near-physiological conditions at single-molecule level. However, interpreting two-dimensional molecular surfaces multiple molecules measured AFM experiments as three-dimensional single molecule poses significant challenge. Here, we present AFMfit, flexible fitting procedure that deforms an input atomic model match observations. The fitted models form ensemble unambiguously...
Abstract We propose to take an artifact‐centric approach design studies by leveraging the concept of boundary object. Design typically focus on processes and articulate decisions in a project‐specific context with goal transferability. argue that could benefit from paying attention material conditions which teams collaborate reach outcomes. report study isochrone maps following cartographic generalization principles. Focusing objects enables us characterize five categories artifacts tools...
Single-particle cryo-electron microscopy (cryo-EM) has been shown to be effective in defining the structure of macromolecules, including protein complexes. Complexes adopt different conformations and compositions perform their biological functions. In cryo-EM, complexes are observed solution, enabling recording images multiple conformations. Various methods exist for capturing conformational variability through analysis cryo-EM data. Here, we analyzed hexameric AAA + ATPase p97, a complex...
Abstract Cryo electron tomography (cryo-ET) allows observing macromolecular complexes in their native environment. The common routine of subtomogram averaging (STA) obtaining the three-dimensional (3D) structure abundant complexes, and can be coupled with discrete classification to reveal conformational heterogeneity sample. However, number extracted from cryo-ET data is usually small, which restricts discrete-classification results a small enough populated states and, thus, largely...
Cryo electron microscopy (cryo-EM) instrumentation allows obtaining 3D reconstruction of the structure biomolecular complexes in vitro (purified studied by single particle analysis) and situ (complexes cells cryo tomography). Standard cryo-EM approaches allow high-resolution only a few conformational states molecular complex, as they rely on data classification into given number classes to increase resolution from few, most populated discard all other classes. Such discrete-classification...
Single particle analysis from cryogenic transmission electron microscopy (cryo-EM) is particularly attractive for complexes which structure prediction remains intractable, such as antibody-antigen complexes. Here we obtain the detailed of a difficult complex between human epidermal growth factor receptor 2 (HER2) and antigen-binding fragments two distinct therapeutic antibodies binding to distant parts flexible HER2, pertuzumab trastuzumab (HTP). We highlight strengths limitations current...
Density volumes obtained by three-dimensional reconstruction of biomolecular complexes from cryogenic electron microscopy (cryo-EM) images (also known as cryo-EM maps) can be interpreted in terms atomic positions flexible fitting. The fitting modifies an available structure to match the target EM map. most accurate methods are based on atomic-coordinate degrees freedom (e.g. Bayesian fitting) but come with high computational cost for large required displacements. To reduce cost, Normal Modes...
Abstract Background The AAA + ATPase p97 is an essential unfoldase/segragase involved in a multitude of cellular processes. It functions as molecular machine critical for protein homeostasis, homotypic membrane fusion events and organelle biogenesis during mitosis which it acts concert with cofactors p47 p37. Cofactors assist extracting unfolding substrates through its ATP hydrolysis. In contrast to p97ʼs cofactors, p37 uniquely increases the activity p97. Disease-causing mutations p97,...
Cryo electron microscopy (cryo-EM) instrumentation allows obtaining 3D reconstruction of the structure biomolecular complexes in vitro (purified studied by single particle analysis) and situ (complexes cells cryo tomography). Standard cryo-EM approaches allow high-resolution only a few conformational states molecular complex, as they rely on data classification into given number classes to increase resolution from most populated while discarding all other classes. Such discrete result...