A5014651890- Cellular Mechanics and Interactions
- Advanced Electron Microscopy Techniques and Applications
- Force Microscopy Techniques and Applications
- Electron and X-Ray Spectroscopy Techniques
- Cardiomyopathy and Myosin Studies
- RNA and protein synthesis mechanisms
- Cell Adhesion Molecules Research
- Cellular transport and secretion
- Advanced Fluorescence Microscopy Techniques
- Lipid Membrane Structure and Behavior
- Enzyme Structure and Function
- Muscle Physiology and Disorders
- RNA modifications and cancer
- Cell Image Analysis Techniques
- Hearing, Cochlea, Tinnitus, Genetics
- Erythrocyte Function and Pathophysiology
- Microtubule and mitosis dynamics
- Heat shock proteins research
- RNA Interference and Gene Delivery
- Photosynthetic Processes and Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Blood properties and coagulation
- Cardiovascular Effects of Exercise
- Monoclonal and Polyclonal Antibodies Research
- Genetics, Aging, and Longevity in Model Organisms
Université Paris Cité
2022-2024
Institut Pasteur
2020-2024
University of California, Santa Barbara
2024
Scintillon Institute
2020-2022
Centre National de la Recherche Scientifique
2022
Laboratoire d’Archéologie Moléculaire et Structurale
2021-2022
Centre de Biologie Structurale
2022
University of Bonn
2021
University of Veterinary Medicine Hannover, Foundation
2021
Discovery Institute
2001-2020
Pulling me apart only makes stronger Tension transmitted between neighboring cells can exert profound effects on cell proliferation, differentiation, and tissue organization. Exactly how intercellular mechanical tension is sensed at the molecular level unknown. One attractive hypothesis that a linkage cell-cell adhesion molecule E-cadherin, its binding partners α- β-catenin, actin filaments may act as sensor. However, this established not known. Buckley et al. used optical tweezers to...
The actin-related protein 2/3 (Arp2/3) complex mediates the formation of branched actin filaments at leading edge motile cells and in comet tails moving certain intracellular pathogens. Crystal structures Arp2/3 are available, but architecture junction formed by base branch was not known. In this study, we use electron tomography to reconstruct with sufficient resolution show how interacts mother filament. Our analysis reveals conformational changes both filament upon formation. Arp2 Arp3...
Although glucose uniquely stimulates proinsulin biosynthesis in β cells, surprisingly little is known of the underlying mechanism(s). Here, we demonstrate that activates unfolded protein response transducer inositol-requiring enzyme 1 alpha (IRE1α) to initiate X-box-binding (Xbp1) mRNA splicing adult primary cells. Using sequencing (mRNA-Seq), show unconventional Xbp1 required increase and decrease expression several hundred mRNAs encoding functions expand secretory capacity for increased...
The seven-subunit Arp2/3 complex choreographs the formation of branched actin networks at leading edge migrating cells. When activated by Wiskott-Aldrich Syndrome protein (WASp), initiates filament branches from sides existing filaments. Electron cryomicroscopy and three-dimensional reconstruction Acanthamoeba castellanii Saccharomyces cerevisiae complexes bound to WASp carboxy-terminal domain reveal asymmetric, oblate ellipsoids. Image analysis indicates that binds side mother filament,...
The crystal structure at 2.0-Å resolution of an 81-residue N-terminal fragment muscle α-tropomyosin reveals a parallel two-stranded α-helical coiled-coil with remarkable core. high alanine content the molecule is clustered into short regions where local 2-fold symmetry broken by small (≈1.2-Å) axial staggering helices. joining these neighboring segments, helices are in register, gives rise to specific bends molecular axis. We observe such be widely distributed proteins. This asymmetric...
Direct continuity between the membranes of cisternae in Golgi complex mammalian cells rarely has been observed; when seen, its documentation equivocal. Here we have used dual-axis electron microscope tomography to examine architecture three dimensions at approximately 6-nm resolution rapidly frozen, freeze-substituted murine that make and secrete insulin response glucose challenge. Our data show types direct connections are normally distinct from one another. These all "bypass" interceding...
Here we report the crystal structure at approximately 4-A resolution of a selectively proteolyzed bovine fibrinogen. This key component in hemostasis is an elongated 340-kDa glycoprotein plasma that upon activation by thrombin self-assembles to form fibrin clot. The crystals are unusual because they made up end-to-end bonded molecules flexible filaments. We have visualized entire coiled-coil region molecule, which has planar sigmoidal shape. primary polymerization receptor pockets ends...
Actin bundles have profound effects on cellular shape, division, adhesion, motility, and signaling. Fimbrin belongs to a large family of actin-bundling proteins is involved in the formation tightly ordered cross-linked brush border microvilli stereocilia inner ear hair cells. Polymorphism these three-dimensional (3D) has prevented detailed structural characterization required for in-depth understanding their morphogenesis function. Here, we describe two-dimensional arrays actin with human...
The actin-binding protein αE-catenin may contribute to transitions between cell migration and cell–cell adhesion that depend on remodeling the actin cytoskeleton, but underlying mechanisms are unknown. We show domain (ABD) binds cooperatively individual filaments binding is accompanied by a conformational change in protomer affects filament structure. ABD limits barbed-end growth, especially bundles. inhibits branching Arp2/3 complex severing cofilin, both of which contact regions...
Actin capping and cross-linking proteins regulate the dynamics architectures of different cellular protrusions. Eps8 is founding member a unique family capable side-binding bundling actin filaments. However, structural basis through which exerts these functions remains elusive. Here, we combined biochemical, molecular, genetic approaches with electron microscopy image analysis to dissect molecular mechanism responsible for distinct activities Eps8. We propose that activity mainly mediated by...
B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax) is a member of the Bcl-2 family having pivotal role in triggering cell commitment to apoptosis. Bax latent and monomeric cytosol but transforms into its lethal, mitochondria-embedded oligomeric form response stress, leading release apoptogenic factors such as cytochrome C. Here, we dissected structural correlates membrane insertion while oligomerization halted. This strategy was enabled through use nanometer-scale phospholipid bilayer...
Abstract Synaptic function depends on interactions among sets of proteins that assemble into complex supramolecular machines. Molecular biology, electrophysiology, and live‐cell imaging studies have provided tantalizing glimpses the inner workings synapse, but fundamental questions remain regarding functional organization these “nano‐machines.” Electron tomography reveals internal structure synapses in three dimensions with exceptional spatial resolution. Here we report results from an...