A5036139273- Ubiquitin and proteasome pathways
- Phagocytosis and Immune Regulation
- Chronic Lymphocytic Leukemia Research
- Cardiomyopathy and Myosin Studies
- Malaria Research and Control
- Trypanosoma species research and implications
- Ion Transport and Channel Regulation
- Plant Gene Expression Analysis
- Membrane-based Ion Separation Techniques
- Ion channel regulation and function
- Muscle Physiology and Disorders
- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- PI3K/AKT/mTOR signaling in cancer
- Plant-derived Lignans Synthesis and Bioactivity
- Force Microscopy Techniques and Applications
- Cell death mechanisms and regulation
- Vestibular and auditory disorders
- Cardiovascular Effects of Exercise
- Medicinal plant effects and applications
- Toxin Mechanisms and Immunotoxins
- Plant Stress Responses and Tolerance
- Cardiovascular Function and Risk Factors
- Plant-Microbe Interactions and Immunity
- Bee Products Chemical Analysis
Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
2020-2024
Université d'Orléans
2015-2024
Sorbonne Université
2022-2024
Institut Curie
2021-2024
Centre National de la Recherche Scientifique
2003-2024
Physiologie, Ecologie et Environnement
2013-2023
Université Paris Sciences et Lettres
2023
Martin Luther University Halle-Wittenberg
2023
Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes
2021
Centre de Biologie Structurale
2003-2018
Abstract Hypertrophic cardiomyopathies (HCM) result from distinct single-point mutations in sarcomeric proteins that lead to muscle hypercontractility. While different models account for a pathological increase the power output, clear understanding of molecular basis dysfunction HCM is mandatory next step improve current treatments. Here, we present an optimized quasi-atomic model sequestered state cardiac myosin coupled X-ray crystallography and silico analysis mechanical compliance lever...
Abstract To save energy and precisely regulate cardiac contractility, muscle myosin heads are sequestered in an ‘off’ state that can be converted to ‘on’ when exertion is increased. The equated with a folded-back structure known as the interacting-heads motif (IHM), which regulatory feature of all class-2 non-muscle myosins. We report here human β-cardiac IHM determined by cryo-electron microscopy 3.6 Å resolution, providing details interfaces stabilizing state. shows these hot spots...
Abstract Inherited cardiomyopathies are common cardiac diseases worldwide, leading in the late stage to heart failure and death. The most promising treatments against these small molecules directly modulating force produced by β-cardiac myosin, molecular motor driving contraction. Omecamtiv mecarbil Mavacamten two such that completed phase 3 clinical trials, inhibitor is now approved FDA. In contrast Mavacamten, acts as an activator of contractility. Here, we reveal X-ray crystallography...
A novel category of major intrinsic proteins which share weak similarities with previously identified aquaporin subfamilies was recently in land plants, and named X (for unrecognized) (XIPs). Because XIPs are still ranked as uncharacterized proteins, their further molecular characterization is required. Herein, a systematic fine-scale analysis XIP sequences found flowering plant databases revealed that at least five groups. The phylogenetic relationship these groups the organization...
Nettle (Urtica dioica L.) is a herbaceous perennial that has been used for centuries in folk medicine. More recently, nettle extracts have also cosmetics because of the many benefits their topical application skin health. Their potential anti-aging action particular interest and primarily ascribed to antioxidant capacity. Here, using an experimental design approach clustering analysis, we linked phytochemical composition biological activities. This confirmed capacity as well providing first...
Abstract Plasmodium parasites are obligate intracellular protozoa and causative agents of malaria, responsible for half a million deaths each year. The lifecycle progression the parasite is reliant on cell motility, process driven by myosin A, an unconventional single-headed class XIV molecular motor. Here we demonstrate that A from falciparum (PfMyoA) critical red blood invasion. Further, using combination X-ray crystallography, kinetics, in vitro motility assays, elucidate non-canonical...
Akt plays a central role in the regulation of cellular anti-apoptosis underlying various human neoplastic diseases. We have demonstrated previously that TCL1 (a proto-oncogene T cell prolymphocytic leukemia) interacts with and functions as an kinase co-activator. With aim to develop inhibitor, we hypothesized peptide, which spans Akt-binding site, binds modulates activity its downstream biological responses. Indeed, named "Akt-in" (Akt NH2-AVTDHPDRLWAWEKF-COOH, encompassing βA strand TCL1),...
Abstract Plasmodium falciparum , the causative agent of malaria, moves by an atypical process called gliding motility. Actomyosin interactions are central to However, details these remained elusive until now. Here, we report atomic structure divergent actomyosin system determined electron cryomicroscopy at end powerstroke (Rigor state). The provides insights into detailed that required for parasite produce force and motion infectivity. Remarkably, footprint myosin motor on filamentous actin...
Parasites from the genus Plasmodium are causative agents of malaria. The mobility, infectivity, and ultimately pathogenesis falciparum rely on a macromolecular complex, called glideosome. At core glideosome is an essential divergent Myosin A motor (PfMyoA), first order drug target against Here, we present full-length structure PfMyoA in two states its cycle. We report novel interactions that for priming mode recognition light chains (PfELC MTIP) by degenerate IQ motifs. Kinetic motility...
Abstract Malaria results in more than 500,000 deaths per year and the causative Plasmodium parasites continue to develop resistance all known agents, including different antimalarial combinations. The class XIV myosin motor PfMyoA is part of a core macromolecular complex called glideosome, essential for parasite mobility therefore an attractive drug target. Here, we characterize interaction small molecule (KNX-002) with PfMyoA. KNX-002 inhibits ATPase activity vitro blocks asexual blood...
Chromosomal translocations leading to overexpression of p14(TCL1) and its homologue p13(MTCP1) are hallmarks several human T-cell malignancies (1). p14(TCL1)/p13(MTCP1) co-activate protein kinase B (PKB, also named Akt) by binding pleckstrin homology (PH) domain, suggesting that induce leukemia promoting anti-apoptotic signals via PKB (2, 3). Here we combined fluorescence anisotropy, NMR, small angle x-ray-scattering measurements determine the affinities, molecular interfaces, low resolution...
Aquaporins are transmembrane water channels found in almost every living organism. Numerous studies have brought a good understanding of both transport through their pores and the regulations taking place at molecular level, but subtleties remain to be clarified. Recently, voltage-related gating mechanism involving conserved arginine channel's main constriction was captured for human aquaporins dynamics studies. With similar approach, we show that this voltage-gating could among family...
Summary Inherited cardiomyopathies are amongst the most common cardiac diseases worldwide, leading in late-stage to heart failure and death. The promising treatments against these small-molecules directly modulating force produced by β-cardiac myosin, molecular motor driving contraction. Two of molecules that produce antagonistic effects on contractility have completed clinical phase 3 trials: activator Omecamtiv mecarbil inhibitor Mavacamten . In this work, we reveal X-ray crystallography...
Previous works have shown the existence of protein partnerships belonging to a MultiStep Phosphorelay (MSP) in Populus putatively involved osmosensing. This study is focused on identification histidine-aspartate kinase, HK1b, paralog HK1a. The characterization HK1b showed its ability homo- and hetero-dimerize interact with few Histidine-containing Phosphotransfer (HPt) proteins, suggesting preferential partnership poplar MSP linked drought perception. Furthermore, determinants for...