@article {2019|2081, title = {Visualizing Biological Membrane Organization and Dynamics.}, journal = {J Mol Biol}, volume = {431}, year = {2019}, month = {2019 05 03}, pages = {1889-1919}, abstract = {

Biological membranes are fascinating. Santiago Ram{\'o}n y Cajal, who received the Nobel prize in 1906 together with Camillo Golgi for their work on the nervous system, wrote \"[\…]in the study of this membrane[\…] I felt more profoundly than in any other subject of study the shuddering sensation of the unfathomable mystery of life\". The visualization and conceptualization of these biological objects have profoundly shaped many aspects of modern biology, drawing inspiration from experiments, computer simulations, and the imagination of scientists and artists. The aim of this review is to provide a fresh look on current ideas of biological membrane organization and dynamics by discussing selected examples across fields.

}, keywords = {Animals, Cell Membrane, Humans, Lipid Bilayers, Microscopy, Atomic Force, Microscopy, Electron, Transmission, Molecular Dynamics Simulation}, issn = {1089-8638}, doi = {10.1016/j.jmb.2019.02.018}, author = {Marc Baaden} } @article {2018|2087, title = {The major β-catenin/E-cadherin junctional binding site is a primary molecular mechano-transductor of differentiation .}, journal = {Elife}, volume = {7}, year = {2018}, month = {2018 07 19}, abstract = {

, the primary molecular mechanotransductive events mechanically initiating cell differentiation remain unknown. Here we find the molecular stretching of the highly conserved Y654-β-catenin-D665-E-cadherin binding site as mechanically induced by tissue strain. It triggers the increase of accessibility of the Y654 site, target of the Src42A kinase phosphorylation leading to irreversible unbinding. Molecular dynamics simulations of the β-catenin/E-cadherin complex under a force mimicking a 6 pN physiological mechanical strain predict a local 45\% stretching between the two α-helices linked by the site and a 15\% increase in accessibility of the phosphorylation site. Both are quantitatively observed using FRET lifetime imaging and non-phospho Y654 specific antibody labelling, in response to the mechanical strains developed by endogenous and magnetically mimicked early mesoderm invagination of gastrulating embryos. This is followed by the predicted release of 16\% of β-catenin from junctions, observed in FRAP, which initiates the mechanical activation of the β-catenin pathway process.

}, keywords = {Amino Acid Sequence, Animals, Armadillo Domain Proteins, Binding Sites, Cadherins, Cell Differentiation, Drosophila melanogaster, Drosophila Proteins, Fluorescence Resonance Energy Transfer, Mechanotransduction, Cellular, Molecular Dynamics Simulation, Phosphorylation, Protein Binding, Protein Conformation, Proto-Oncogene Proteins pp60(c-src), Sequence Homology, Transcription Factors}, issn = {2050-084X}, doi = {10.7554/eLife.33381}, author = {R{\"o}per, Jens-Christian and Mitrossilis, D{\'e}mosth{\`e}ne and Guillaume Stirnemann and Waharte, Fran{\c c}ois and Brito, Isabel and Fernandez-Sanchez, Maria-Elena and Marc Baaden and Salamero, Jean and Farge, Emmanuel} } @article {2017|2030, title = {Why Is Research on Amyloid-β Failing to Give New Drugs for Alzheimer{\textquoteright}s Disease?}, journal = {ACS Chem Neurosci}, volume = {8}, year = {2017}, month = {2017 Jul 19}, pages = {1435-1437}, abstract = {

The two hallmarks of Alzheimer\&$\#$39;s disease (AD) are the presence of neurofibrillary tangles (NFT) made of aggregates of the hyperphosphorylated tau protein and of amyloid plaques composed of amyloid-β (Aβ) peptides, primarily Aβ1-40 and Aβ1-42. Targeting the production, aggregation, and toxicity of Aβ with small molecule drugs or antibodies is an active area of AD research due to the general acceptance of the amyloid cascade hypothesis, but thus far all drugs targeting Aβ have failed. From a review of the recent literature and our own experience based on in vitro, in silico, and in vivo studies, we present some reasons to explain this repetitive failure.

}, keywords = {Alzheimer Disease, Amyloid beta-Peptides, Animals, Drug Discovery, Humans, Neuroprotective Agents}, issn = {1948-7193}, doi = {10.1021/acschemneuro.7b00188}, author = {Doig, Andrew J and Del Castillo-Frias, Maria P and Berthoumieu, Olivia and Tarus, Bogdan and Nasica-Labouze, Jessica and Sterpone, Fabio and Phuong Hoang Nguyen and Hooper, Nigel M and Faller, Peter and Philippe Derreumaux} } @article {2014|1792, title = {Allosteric regulation of pentameric ligand-gated ion channels: An emerging mechanistic perspective}, journal = {Channels}, volume = {8}, number = {4}, year = {2014}, pages = {350{\textendash}360}, keywords = {Allosteric Regulation, Animals, chemistry/metabolism, Humans, Ion Channel Gating, Ligand-Gated Ion Channels, metabolism, Models, Molecular, Protein Multimerization, Small Molecule Libraries}, author = {Antoine Taly and J{\'e}r{\^o}me H{\'e}nin and Changeux, Jean-Pierre and Cecchini, Marco} } @article {2010|1789, title = {Single-spanning transmembrane domains in cell growth and cell-cell interactions: More than meets the eye?}, journal = {Cell Adh. Migr.}, volume = {4}, number = {2}, year = {2010}, month = {apr}, pages = {313{\textendash}324}, abstract = {

As a whole, integral membrane proteins represent about one third of sequenced genomes, and more than 50\% of currently available drugs target membrane proteins, often cell surface receptors. Some membrane protein classes, with a defined number of transmembrane (TM) helices, are receiving much attention because of their great functional and pharmacological importance, such as G protein-coupled receptors possessing 7 TM segments. Although they represent roughly half of all membrane proteins, bitopic proteins (with only 1 TM helix) have so far been less well characterized. Though they include many essential families of receptors, such as adhesion molecules and receptor tyrosine kinases, many of which are excellent targets for biopharmaceuticals (peptides, antibodies, et al.). A growing body of evidence suggests a major role for interactions between TM domains of these receptors in signaling, through homo and heteromeric associations, conformational changes, assembly of signaling platforms, etc. Significantly, mutations within single domains are frequent in human disease, such as cancer or developmental disorders. This review attempts to give an overview of current knowledge about these interactions, from structural data to therapeutic perspectives, focusing on bitopic proteins involved in cell signaling.

}, keywords = {Animals, Biological, Humans, Membrane Proteins, Models, Protein Structure, Secondary, Signal Transduction, Tertiary}, issn = {1933-6926}, doi = {10.4161/cam.4.2.12430}, author = {Pierre Hubert and Paul Sawma and Jean-Pierre Duneau and Jonathan Khao and J{\'e}r{\^o}me H{\'e}nin and Dominique Bagnard and James Sturgis} } @article {2006|1935, title = {HDAC1 acetylation is linked to progressive modulation of steroid receptor-induced gene transcription.}, journal = {Mol. Cell}, volume = {22}, number = {5}, year = {2006}, month = {jun}, pages = {669{\textendash}679}, publisher = {Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Building 41, B602, Bethesda, Maryland 20892, USA.}, abstract = {Although histone deacetylases (HDACs) are generally viewed as corepressors, we show that HDAC1 serves as a coactivator for the glucocorticoid receptor (GR). Furthermore, a subfraction of cellular HDAC1 is acetylated after association with the GR, and this acetylation event correlates with a decrease in promoter activity. HDAC1 in repressed chromatin is highly acetylated, while the deacetylase found on transcriptionally active chromatin manifests a low level of acetylation. Acetylation of purified HDAC1 inactivates its deacetylase activity, and mutation of the critical acetylation sites abrogates HDAC1 function in vivo. We propose that hormone activation of the receptor leads to progressive acetylation of HDAC1 in vivo, which in turn inhibits the deacetylase activity of the enzyme and prevents a deacetylation event that is required for promoter activation. These findings indicate that HDAC1 is required for the induction of some genes by the GR, and this activator function is dynamically modulated by acetylation.}, keywords = {Acetylation, Amino Acid Sequence, Animals, Binding Sites, Cell Cycle Proteins, Chromatin, Down-Regulation, genetics/metabolism, Hela Cells, Histone Acetyltransferases, Histone Deacetylases, Humans, immunology/metabolism, metabolism}, doi = {10.1016/j.molcel.2006.04.019}, author = {Yi Qiu and Yingming Zhao and Matthias Becker and Sam John and Bhavin S Parekh and Suming Huang and Anindya Hendarwanto and Elisabeth D Martinez and Yue Chen and Hanxin Lu and Nicholas L Adkins and Diana A Stavreva and Malgorzata Wiench and Philippe T Geor} } @article {2005|1775, title = {Chromatin remodeling complexes: ATP-dependent machines in action.}, journal = {Biochem. Cell Biol.}, volume = {83}, number = {4}, year = {2005}, month = {aug}, pages = {405{\textendash}417}, publisher = {Division of Biological Sciences, Marshall University, Huntington, WV 25755, USA.}, abstract = {Since the initial characterization of chromatin remodeling as an ATP-dependent process, many studies have given us insight into how nucleosome-remodeling complexes can affect various nuclear functions. However, the multistep DNA-histone remodeling process has not been completely elucidated. Although new studies are published on a nearly weekly basis, the nature and roles of interactions of the individual SWI/SNF- and ISWI-based remodeling complexes and DNA, core histones, and other chromatin-associated proteins are not fully understood. In addition, the potential changes associated with ATP recruitment and its subsequent hydrolysis have not been fully characterized. This review explores possible mechanisms by which chromatin-remodeling complexes are recruited to specific loci, use ATP hydrolysis to achieve actual remodeling through disruption of DNA-histone interactions, and are released from their chromatin template. We propose possible roles for ATP hydrolysis in a chromatin-release/target-scanning process that offer an alternative to or complement the often overlooked function of delivering the energy required for sliding or dislodging specific subsets of core histones.}, keywords = {Adenosine Triphosphatases, Adenosine Triphosphate, Animals, Chromatin, Gene Expression Regulation, genetics/metabolism, Humans, metabolism, Nucleosomes, Transcription Factors}, doi = {10.1139/o05-115}, author = {Cotteka N Johnson and Nicholas L Adkins and Philippe Georgel} } @article {1994|1968, title = {Three-dimensional structure of extended chromatin fibers as revealed by tapping-mode scanning force microscopy}, journal = {Proc. Natl. Acad. Sci. U.s.a.}, volume = {91}, number = {24}, year = {1994}, month = {nov}, pages = {11621{\textendash}11625}, abstract = {Unfixed chicken erythrocyte chromatin fibers in very low salt have been imaged with a scanning force microscope operating in the tapping mode in air at ambient humidity. These images reveal a three-dimensional organization of the fibers. The planar "zig-zag" conformation is rare, and extended "beads-on-a-string" fibers are seen only in chromatin depleted of histones H1 and H5. Glutaraldehyde fixation reveals very similar structures. Fibers fixed in 10 mM salt appear somewhat more compacted. These results, when compared with modeling studies, suggest that chromatin fibers may exist as irregular three-dimensional arrays of nucleosomes even at low ionic strength.}, keywords = {Animals, Atomic Force, Biological, Chickens, Chromatin, Fixatives, Histones, Microscopy, Models, Non-P.H.S., Non-U.S. Gov{\textquoteright}t, Osmolar Concentration, P.H.S., Research Support, Sodium Chloride, U.S. Gov{\textquoteright}t}, author = {S. H. Leuba and G. Yang and C. Robert and B. Samori and K. van Holde and J. Zlatanova and C. Bustamante} }