Article
Multidisciplinary Sciences
Alisa Cario, Adriana Savastano, Neil B. Wood, Zhu Liu, Michael J. Previs, Adam G. Hendricks, Markus Zweckstetter, Christopher L. Berger
Summary: Contrary to the canonical disease-state theory, the R5L mutation in Tau does not reduce its affinity for microtubules but decreases its ability to form larger-order complexes at high concentrations. This mutation results in a local structural change in Tau's projection domain.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Multidisciplinary
Adriana Savastano, David Flores, Harindranath Kadavath, Jacek Biernat, Eckhard Mandelkow, Markus Zweckstetter
Summary: Phosphorylation of tau at specific epitopes can affect its ability to nucleate microtubule bundles during LLPS, while phosphorylation at other sites does not inhibit tubulin assembly from tau droplets. This suggests that IDP phosphorylation may be a widely used mechanism for regulating condensate-mediated cytoskeletal assembly.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Neurosciences
Francois-Xavier Cantrelle, Anne Loyens, Xavier Trivelli, Oliver Reimann, Clement Despres, Neha S. Gandhi, Christian P. R. Hackenberger, Isabelle Landrieu, Caroline Smet-Nocca
Summary: Phosphorylation of Tau protein plays a critical role in the aggregation process observed in Alzheimer's disease brains. Recent research has highlighted the regulatory role of O-GlcNAcylation in modulating Tau phosphorylation and aggregation. Results showed that O-GlcNAcylation reduces phosphorylation of PHF-1 epitope, which is hyperphosphorylated in AD brains, and impacts the rate of fibrillar assembly in in-vitro assays.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Chemistry, Multidisciplinary
Dmitry M. Lesovoy, Panagiota S. Georgoulia, Tammo Diercks, Irena Matecko-Burmann, Bjorn M. Burmann, Eduard Bocharov, Wolfgang Bermel, Vladislav Y. Orekhov
Summary: This study introduces a sensitive and robust alternative method for rapid local assignment near affected signals in intrinsically disordered proteins (IDPs), based on FOcused SpectroscopY (FOSY) experiments using selective polarisation transfer (SPT). The efficiency of this method is demonstrated by identifying two phosphorylation sites of glycogen synthase kinase 3 beta (GSK3 beta) in human Tau40, an IDP of 441 residues, and revealing unprimed phosphorylation of Ser409. This approach may benefit NMR studies of post-translational modifications (PTMs) and hotspots in IDPs involved in molecular interactions.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Physical
Clayton J. Dahlman, Rhys M. Kennard, Piotr Paluch, Naveen R. Venkatesan, Michael L. Chabinyc, G. N. Manjunatha Reddy
Summary: Layered hybrid organic-inorganic perovskites, such as the lead halide Ruddlesden-Popper (RP) series, exhibit tunable optoelectronic properties due to dynamic interactions between the ionic perovskite substructure and organic spacer cations. Solid-state NMR spectroscopy was used to characterize the static and dynamic structures of linear alkylammonium and aromatic spacers in lead iodide RP phases, revealing different site-specific rigidity trends for short and long spacers. The study highlights the interplay between spacer interactions with lead iodide octahedra and van der Waals forces in contributing to a variety of site-specific dynamics and structural distortions at intermediate time scales.
CHEMISTRY OF MATERIALS
(2021)
Article
Biology
Tetsuya Hori, Kohgaku Eguchi, Han-Ying Wang, Tomohiro Miyasaka, Laurent Guillaud, Zacharie Taoufiq, Satyajit Mahapatra, Hiroshi Yamada, Kohji Takei, Tomoyuki Takahashi, Nils Brose
Summary: This study found that soluble wild-type tau accumulates in synaptic compartments in Alzheimer's disease, and its accumulation affects synaptic transmission. Tau accumulation leads to microtubule assembly and activity-dependent rundown of excitatory neurotransmission.
Article
Chemistry, Physical
Luiz Schubert, Pit Langner, David Ehrenberg, Victor A. Lorenz-Fonfria, Joachim Heberle
Summary: Mid-IR spectroscopy is used to investigate protein reactions. In this study, quantum-cascade-laser-based dual-comb spectroscopy is used to probe protein conformational changes and protonation events by a single-shot experiment. The feasibility of QCL-based infrared spectroscopy in monitoring irreversible reactions is demonstrated.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Chemistry, Multidisciplinary
Robert Lassfolk, Manuel Pedron, Tomas Tejero, Pedro Merino, Johan Warna, Reko Leino
Summary: Acyl group migration plays a significant role in the synthesis, isolation, manipulation and purification of acylated organic compounds containing free hydroxyl groups, especially carbohydrates. Our study reveals that the anomeric configuration in monosaccharides, along with the relative configurations of other hydroxyl groups and the properties of the migrating acyl group, greatly influence the migration rate.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Himanshu Singh, Chandan K. Das, Benjamin C. Buchmuller, Lars Schaefer, Daniel Summerer, Rasmus Linser
Summary: Researchers have discovered that 5-methylcytosine (mC) and its TET-oxidized derivatives exist in CpG dyads of mammalian DNA and regulate cell fate, but how they function as distinct regulatory signals is not well understood. Designing readers that selectively recognize these novel 'CpG duplex marks' presents a challenge due to their unprecedented selectivity requirements. This study demonstrates the importance of precise conformational plasticity for the selectivity of a designer reader for an oxidized CpG duplex mark.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Neurosciences
Maria J. Benitez, Raquel Cuadros, Juan S. Jimenez
Summary: The study suggests that the catalytic subunit of PKA can catalyze both phosphorylation and dephosphorylation of tau protein, depending on the ATP/ADP ratio. These findings contribute to understanding the relationship between the compartmentalized energy state of neurons and disruptions in mitochondrial functions with tau-related pathologies.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Materials Science, Multidisciplinary
D. Koumoulis, J. P. Scheifers, B. P. T. Fokwa, L. -s. Bouchard
Summary: The ordering of boron in the Sc2Ir6-xNixB series of intermetallic borides is affected by Ni substitution, as studied using 11B-NMR. The substitution of Ni leads to phase separation at the nanoscale between ordered and disordered borides. The behavior of the boron impurities at x = 3 and x = 5 is characterized by different temperature dependencies of the spin-lattice relaxation rates (T_ 1 1 ), indicating different relaxation mechanisms.
MATERIALS RESEARCH BULLETIN
(2023)
Article
Nanoscience & Nanotechnology
Hendrik Spende, Christoph Margenfeld, Andreas Waag
Summary: This study proposes GaN/AlGaN core-shell microfins as a model system to demonstrate the efficiency potential of ultra-low-defect nonpolar UV emitters. By using selective-area metalorganic vapor phase epitaxy, mostly crack-free AlGaN quantum wells with a low threading dislocation density could be realized. The carrier dynamics within the nonpolar AlGaN structures were studied, and the internal quantum efficiency of the studied sample was estimated to be around 40% at room temperature.
Review
Pharmacology & Pharmacy
Majedul Islam, Fengyun Shen, Deepika Regmi, Deguo Du
Summary: Tauopathies are neurodegenerative diseases characterized by abnormal tau deposition in the brain. Currently, there are no approved disease-modifying therapies for tauopathies. Drug repurposing offers a potential alternative approach to discover effective drugs for treating these diseases.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Francesca Parolini, Elham Ataie Kachoie, Giulia Leo, Laura Civiero, Luigi Bubacco, Giorgio Arrigoni, Francesca Munari, Michael Assfalg, Mariapina D'Onofrio, Stefano Capaldi
Summary: Post-translational modifications of Tau play an important role in the onset and progression of tauopathies like Alzheimer's disease. The E3 ligase CHIP has been shown to catalyze the ubiquitination of Tau filaments in vitro and in cellular models. The conformation of Tau amyloids restricts the site-specific ubiquitination to specific positions of the repeat domain, while fibril core structure remains largely unaffected. Overexpression of CHIP promotes ubiquitination of Tau aggregates in complex cellular environments.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Multidisciplinary Sciences
Han Pan, Ruifang Guan, Ruixue Zhao, Guangshuo Ou, Zhucheng Chen
Summary: The central spindle in animal cells regulates the formation of the division plane during cytokinesis. The molecular backbone of centralspindlin has the propensity to undergo liquid-liquid phase separation, and the synergy between ZEN-4 and CYK-4 subunits is critical for its function in microtubule bundling and central spindle assembly. Charge-driven macromolecular condensation mediates the assembly of the central spindle by centralspindlin.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Joao Filipe Neves, Olivia Petrvalska, Francesco Bosica, Francois-Xavier Cantrelle, Hamida Merzougui, Gavin O'Mahony, Xavier Hanoulle, Tomas Obsil, Isabelle Landrieu
Summary: Protein-protein interactions (PPIs) involving 14-3-3 proteins and Tau are potential targets for Alzheimer's disease treatment. Phosphorylation of Tau by PKA is crucial for the formation of a stable complex with 14-3-3 sigma, with an affinity in the 1-10 micromolar range. Each monomer of the 14-3-3 sigma dimer binds to two different phosphorylated peptides of Tau-PKA, suggesting a 2:1 stoichiometry for 14-3-3/Tau-PKA.
Article
Chemistry, Analytical
Neil Cox, Pierre Millard, Cyril Charlier, Guy Lippens
Summary: Phosphorylated metabolites are widespread in cells, and an improved NMR workflow has been detailed for assigning their high-resolution subspectrum in complex mixtures. By combining various experimental techniques, selective identification of individual subspectra of phosphorylated metabolites can be achieved efficiently.
ANALYTICAL CHEMISTRY
(2021)
Article
Cell Biology
Rie Ayukawa, Seigo Iwata, Hiroshi Imai, Shinji Kamimura, Masahito Hayashi, Kien Xuan Ngo, Itsushi Minoura, Seiichi Uchimura, Tsukasa Makino, Mikako Shirouzu, Hideki Shigematsu, Ken Sekimoto, Benoit Gigant, Etsuko Muto
Summary: This study demonstrates that the formation of straight oligomers of critical size is essential for nucleation of microtubules. Both GDP and GTP tubulin form single-stranded oligomers with different curvature distributions, and the proportion of straight oligomers can accelerate nucleation. The results suggest that cellular factors involved in nucleation promote it via stabilization of straight oligomers.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Paloma F. Varela, Melanie Chenon, Christophe Velours, Kristen J. Verhey, Julie Menetrey, Benoit Gigant
Summary: Motile kinesins are motor proteins that move along microtubules by hydrolyzing ATP. This study provides structural insights into the nucleotide cycle of OSM-3, demonstrating a shared ATPase mechanism similar to that of Eg5 in the kinesin superfamily.
Article
Multidisciplinary Sciences
Anastasiia Grigoreva, Julia Andreeva, Dmitry Bikmetov, Anastasiia Rusanova, Marina Serebryakova, Andrea Hernandez Garcia, Darya Slonova, Satish K. Nair, Guy Lippens, Konstantin Severinov, Svetlana Dubiley
Summary: A new family of class III lanthipeptides from Firmicutes is described, with representative member andalusicin showing bioactivity against various Gram-positive bacteria, which is highly dependent on the alpha-N dimethylation.
Article
Chemistry, Analytical
Pierre Millard, Serguei Sokol, Michael Kohlstedt, Christoph Wittmann, Fabien Letisse, Guy Lippens, Jean-Charles Portais
Summary: Stable-isotope labeling experiments are commonly used to investigate metabolic networks, but there is a lack of framework to deal with partial, heterogeneous isotopic measurements. By integrating measurements obtained by different methods, researchers can improve coverage and analysis of isotopic space.
ANALYTICAL CHEMISTRY
(2021)
Article
Neurosciences
Francois-Xavier Cantrelle, Anne Loyens, Xavier Trivelli, Oliver Reimann, Clement Despres, Neha S. Gandhi, Christian P. R. Hackenberger, Isabelle Landrieu, Caroline Smet-Nocca
Summary: Phosphorylation of Tau protein plays a critical role in the aggregation process observed in Alzheimer's disease brains. Recent research has highlighted the regulatory role of O-GlcNAcylation in modulating Tau phosphorylation and aggregation. Results showed that O-GlcNAcylation reduces phosphorylation of PHF-1 epitope, which is hyperphosphorylated in AD brains, and impacts the rate of fibrillar assembly in in-vitro assays.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Chemistry, Multidisciplinary
Francois-Xavier Cantrelle, Emmanuelle Boll, Lucile Brier, Danai Moschidi, Sandrine Belouzard, Valerie Landry, Florence Leroux, Frederique Dewitte, Isabelle Landrieu, Jean Dubuisson, Benoit Deprez, Julie Charton, Xavier Hanoulle
Summary: The study utilized NMR spectroscopy to analyze the conformation of the main protease (3CLp) of SARS-CoV-2 and conducted fragment-based screening to identify inhibitors. This research sheds light on the development of potent 3CLp inhibitors.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biotechnology & Applied Microbiology
Clement Danis, Elian Dupre, Orgeta Zejneli, Raphaelle Caillierez, Alexis Arrial, Severine Begard, Justine Mortelecque, Sabiha Eddarkaoui, Anne Loyens, Francois-Xavier Cantrelle, Xavier Hanoulle, Jean-Christophe Rain, Morvane Colin, Luc Buee, Isabelle Landrieu
Summary: The study demonstrates the effectiveness of VHH Z70 in inhibiting Tau aggregation and reducing pathological Tau accumulation in brain neurons. By specifically targeting Tau within cells, VHH Z70 provides an immunological tool for targeting the intra-cellular compartment in tauopathies.
Article
Multidisciplinary Sciences
Guilherme G. Moreira, Francois-Xavier Cantrelle, Andrea Quezada, Filipa S. Carvalho, Joana S. Cristovao, Urmi Sengupta, Nicha Puangmalai, Ana P. Carapeto, Mario S. Rodrigues, Isabel Cardoso, Guenter Fritz, Federico Herrera, Rakez Kayed, Isabelle Landrieu, Claudio M. Gomes
Summary: The study demonstrates that S100B protein acts as an extracellular chaperone for Tau, inhibiting its aggregation and providing evidence for neuro-protective functions.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Andreas Stein, Persefoni Hilken Nee Thomopoulou, Corazon Frias, Sina M. Hopff, Paloma Varela, Nicola Wilke, Arul Mariappan, Jorg-Martin Neudoerfl, Alexey Yu Fedorov, Jay Gopalakrishnan, Benoit Gigant, Aram Prokop, Hans-Gunther Schmalz
Summary: The synthesis and investigation of PT-100, a potential anticancer drug, were reported. PT-100 exhibited high antiproliferative and apoptosis-inducing effects, especially in multidrug-resistant cancer cell lines, and showed synergistic effects with vincristine in certain cell lines.
Article
Multidisciplinary Sciences
Valerie Campanacci, Agathe Urvoas, Liza Ammar Khodja, Magali Aumont-Nicaise, Magali Noiray, Sylvie Lachkar, Patrick A. Curmi, Philippe Minard, Benoit Gigant
Summary: The study demonstrates the binding of CPAP's PN2-3 domain with tubulin and the similarity in binding mode with fungal and bacterial inhibitors. This finding uncovers the characteristic features of cellular partners binding to this site and highlights the structural convergence of CPAP with small-molecule inhibitors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Chemistry, Multidisciplinary
Isabelle Landrieu, Elian Dupre, Davy Sinnaeve, Lea El Hajjar, Caroline Smet-Nocca
Summary: Protein aggregation into amyloid fibrils is associated with human disorders and the mechanisms and co-factors involved in amyloid formation are still poorly understood. The role of amyloid fibrils in neurodegenerative diseases remains to be elucidated and finding drugs or therapies targeting amyloid formation is challenging. Chemical biology tools and protein engineering methods provide new insights into amyloid formation.
FRONTIERS IN CHEMISTRY
(2022)
Article
Biophysics
Cyril Charlier, Sabine Gavalda, Vinciane Borsenberger, Sophie Duquesne, Alain Marty, Vincent Tournier, Guy Lippens
Summary: Plastic environmental pollution is a major issue. Plastic recycling and degrading enzymes can play an important role in the circular economy.
BIOPHYSICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Alessia Lasorsa, Krishnendu Bera, Idir Malki, Elian Dupre, Francois-Xavier Cantrelle, Hamida Merzougui, Davy Sinnaeve, Xavier Hanoulle, Jozef Hritz, Isabelle Landrieu
Summary: Phosphorylation of Tau protein is associated with Alzheimer's disease progression, and the interaction between Tau and BIN1 is modulated by phosphorylation. Nuclear magnetic resonance spectroscopy studies show that phosphorylation affects the local structure and dynamics of Tau peptide, which in turn affects the binding with BIN1.