A5034114577- Microtubule and mitosis dynamics
- 14-3-3 protein interactions
- Monoclonal and Polyclonal Antibodies Research
- Cellular transport and secretion
- Photosynthetic Processes and Mechanisms
- Ubiquitin and proteasome pathways
- Glycosylation and Glycoproteins Research
- Chemical Synthesis and Analysis
- Protein purification and stability
- Cancer Treatment and Pharmacology
- Cellular Mechanics and Interactions
- Synthesis and biological activity
- Influenza Virus Research Studies
- Respiratory viral infections research
- Cancer therapeutics and mechanisms
- Hepatitis C virus research
- Hepatitis B Virus Studies
- Click Chemistry and Applications
- Herpesvirus Infections and Treatments
- Protein Tyrosine Phosphatases
- Intramuscular injections and effects
- Protein Structure and Dynamics
- Peptidase Inhibition and Analysis
- Genomics, phytochemicals, and oxidative stress
- Alzheimer's disease research and treatments
Institut de Biologie Intégrative de la Cellule
2015-2025
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2016-2025
Centre National de la Recherche Scientifique
2016-2025
Université Paris-Saclay
2016-2025
CEA Paris-Saclay
2016-2025
Université Paris-Sud
1994-2019
Laboratoire d'Enzymologie et Biochimie Structurales
2004-2014
Inserm
2005
Institut du Fer à Moulin
2005
Sorbonne Université
2005
Structural changes occur in the alphabeta-tubulin heterodimer during microtubule assembly/disassembly cycle. Their most prominent feature is a transition from straight, microtubular structure to curved structure. There broad range of small molecule compounds that disturbs cycle, class which targets colchicine-binding site and prevents assembly. This includes with very different chemical structures, it presently unknown whether they prevent tubulin polymerization by same mechanism. To address...
Microtubules are dynamic assemblies of αβ‐tubulin heterodimers and have been recognized as highly attractive targets for cancer chemotherapy. A broad range agents bind to tubulin interfere with microtubule assembly. Despite having a long history characterization, colchicine binding site inhibitors ( CBSI s) not yet reached the commercial phase anti‐cancer drugs date. We determined structures complexed set structurally diverse s (lexibulin, nocodazole, plinabulin tivantinib), among which...
Centrioles are microtubule-based organelles required for the formation of centrosomes and cilia. Centriolar microtubules, unlike their cytosolic counterparts, stable grow very slowly, but underlying mechanisms poorly understood. Here, we reconstituted in vitro interplay between proteins that cap distal centriole ends control elongation: CP110, CEP97, CPAP/SAS-4. We found whereas CEP97 does not bind to microtubules directly, CP110 autonomously binds microtubule plus ends, blocks growth,...
Microtubules are cytoskeleton filaments consisting of αβ-tubulin heterodimers. They switch between phases growth and shrinkage. The underlying mechanism this property, called dynamic instability, is not fully understood. Here, we identified a designed ankyrin repeat protein (DARPin) that interferes with microtubule assembly in unique manner. X-ray structure its complex GTP-tubulin shows it binds to the β-tubulin surface exposed at (+) ends. details provide insight into role GTP...
Abstract Microtubules are pivotal in diverse cellular functions encompassing cell signaling, morphology, intracellular trafficking, and mitosis/division. They validated targets for disease treatment, notably hematological cancers solid tumors. Microtubule‐targeting agents (MTAs) exert their effects by modulating microtubule dynamics, impeding proliferation, promoting death. Recent advances structural biology have unveiled novel perspectives investigating multiple binding sites mechanisms of...
Kinesin-13s are critical microtubule regulators which induce disassembly in an ATP dependent manner. To clarify their mechanism, we report here the crystal structure of a functional construct kinesin-13 Kif2C/MCAK ATP-like state and bound to αβ-tubulin heterodimer, complex mimicking species that dissociates from ends during catalytic disassembly. Our results picture how Kif2C stabilizes curved tubulin conformation. The α4-L12-α5 region undergoes remarkable 25° rotation upon binding target...
Abstract As a major component of the cytoskeleton, microtubules consist αβ-tubulin heterodimers and have been recognized as attractive targets for cancer chemotherapy. Microtubule-stabilizing agents (MSAs) promote polymerization tubulin stabilize polymer, preventing depolymerization. The molecular mechanisms by which MSAs remain elusive. Here we report 2.05 Å crystal structure complexed with taccalonolide AJ, newly identified taxane-site MSA. Taccalonolide AJ covalently binds to β-tubulin...
Vinca-domain ligands are compounds that bind to tubulin at its inter-heterodimeric interface and favour heterogeneous protofilament-like assemblies, giving rise helices rings. This is the basis for their inhibition of microtubule assembly, antimitotic activities use in anticancer chemotherapy. Ustiloxins vinca-domain with a well established total synthesis. A 2.7 Å resolution structure ustiloxin D bound vinca domain embedded complex two tubulins stathmin-like RB3 (T2R) has been determined....
Tau is a microtubule-associated protein that stabilizes microtubules and stimulates their assembly. Current descriptions of the tubulin-interacting regions involve as target result mainly from deletions domains based on sequence analysis NMR spectroscopy experiments. Here, instead microtubules, we use complex two tubulin heterodimers with stathmin-like domain RB3 (T2R) to identify interacting fragments generated by limited proteolysis. We show in proline-rich region microtubule-binding...
We report the synthesis and metabolic biological evaluation of a series 17 novel heterocyclic derivatives isocombretastatin-A4 (iso-CA-4) their structure-activity relationships. Among these derivatives, most active compound, 4f, inhibited growth panel seven cancer cell lines with an IC50 in low nanomolar range. In addition, 4f showed interesting activity against CA-4-resistant colon-carcinoma cells multidrug-resistant leukemia cells. It also induced G2/M cell-cycle arrest. Structural data...
Nucleation of microtubules (MTs) is essential for cellular activities, but its mechanism unknown because the difficulty involved in capturing rare stochastic events early stage polymerization. Here, combining rapid flush negative stain electron microscopy (EM) and kinetic analysis, we demonstrate that formation straight oligomers critical size nucleation. Both GDP GTP tubulin form single-stranded with a broad range curvatures, upon nucleation, curvature distribution shifted to produce minor...
The x-ray structures of three esterase-like catalytic antibodies identified by screening for activity the entire hybridoma repertoire, elicited in response to a phosphonate transition state analog (TSA) hapten, were analyzed. high resolution account catalysis stabilization, and all tyrosine residue participates oxyanion hole. Despite significant conformational differences their combining sites, antibodies, which are most efficient among those elicited, achieve essentially same mode,...