Accueil > Research > Highlights > Archives > 2018
How to control a reactive radical species
Radical S-Adenosyl-l-methionine Tryptophan Lyase (NosL) : How the Protein Controls the Carboxyl Radical •CO2- Migration. Amara P, Mouesca JM, Bella M, Martin L, Saragaglia C, Gambarelli S, Nicolet Y. J Am Chem Soc. 2018 Nov 16. doi : 10.1021/jacs.8b09142 |
The main target of HIV studied from every angle
CCR5 structural plasticity shapes HIV-1 phenotypic properties. Colin P, Zhou Z, Staropoli I, Garcia-Perez J, Gasser R, Armani-Tourret M, Benureau Y, Gonzalez N, Jin J, Connell BJ, Raymond S, Delobel P, Izopet J, Lortat-Jacob H, Alcami J, Arenzana-Seisdedos F, Brelot A, Lagane B. PLoS Pathog. 2018 Dec 6 ;14(12):e1007432. doi : 10.1371/journal.ppat.1007432. eCollection 2018 Dec. |
Innate immune protein C1q aggregates nanodiamonds and modifies macrophage response
Recognition protein C1q of innate immunity agglutinates nanodiamonds without activating complement. Belime A, Thielens NM, Gravel E, Frachet P, Ancelet S, Tacnet P, Caneiro C, Chuprin J, Gaboriaud C, Schoehn G, Doris E, Ling WL. Nanomedicine-Nanotechnology, Biology and Medicine ; doi : 10.1016/j.nano.2018.09.009 |
Chromatin without a twist
Structure of an H1-bound 6-nucleosome array reveals an untwisted two-start chromatin fiber conformation. Isabel Garcia-Saez, Hervé Menoni, Ramachandran Boopathi, Manu S. Shukla, Lama Soueidan, Marjolaine Noirclerc-Savoye, Aline Le Roy, Dimitrios A. Skoufias, Jan Bednar, Ali Hamiche, Dimitar Angelov, Carlo Petosa, Stefan Dimitrov. Molecular Cell, doi : 10.1016/j.molcel.2018.09.027. |
A key step in mitochondrial biogenesis revealed by structural biology
Structural Basis of Membrane Protein Chaperoning Through the Mitochondrial Intermembrane Space. Katharina Weinhäupl, Caroline Lindau, Audrey Hessel, Yong Wang, Conny Schütze, Tobias Jores, Laura Melchionda, Birgit Schönfisch, Hubert Kalbacher, Beate Bersch, Doron Rapaport, Martha Brennich, Kresten Lindorff-Larsen, Nils Wiedemann, Paul Schanda. Cell 175, 1365–1379 |
Cécile Morlot is the recipient of the CNRS bronze medalCécile Morlot (IBS/Pneumococcus group) is the recipient of a bronze medal of the CNRS 2018. This distinction rewards an on-going and fruitful research activity, which makes him/her a specialist with talent within a particular research field.
She is recruited by the CNRS in 2010 and joins the Pneumococcus group at the IBS to continue her research activities on bacterial morphogenesis and division, using complementary techniques in structural and cellular biology. Her recruitment coincides with the emergence of super-resolution fluorescence microscopy techniques, which allow connecting protein and cellular scales. She decides to develop the use of these techniques in the pneumococcus in collaboration with biophysicists from the IBS (Dominique Bourgeois and Virgile Adam, Pixel team) and a chemist from the University Grenoble Alpes (Yung-Sing Wong, Department of Molecular Pharmacochemistry). The developed methods, based on the localization of single molecules and on "click chemistry", now allow her to image the assembly and activity of protein machineries in charge of cell division at a resolution of about ten nanometers. Because it reveals molecular details that are inaccessible at low resolution, her work in structural biology and cell imaging helps understanding how bacteria acquire their shape and proliferate. This fundamental knowledge is pertinent for the discovery of new antibiotics and for the comprehension of associated resistance mechanisms. |
New insights into 5-HT3, a serotonin receptor
Scientists from the IBS, the Institut Pasteur, the University of Lorraine, the University of Copenhagen, Danemark, the University of Illinois, US, and the biotech company Theranyx, solved the structure of the 5-HT3 receptor in four different conformations. These four snapshots taken at different steps of the activation cycle of the receptor allow to describe its molecular mechanism. They also provide structural knowledge for pharmacology, revealing details of the serotonin and drug binding site, and may therefore help the development of more efficient anti-emetics (see ESRF press release). Conformational transitions of the serotonin 5-HT3 receptor. Lucie Polovinkin, Ghérici Hassaine, Jonathan Perot, Emmanuelle Neumann, Anders A. Jensen, Solène Lefebvre, Pierre-Jean Corringer, Jacques Neyton, Christophe Chipot, Francois Dehez, Guy Schoehn & Hugues Nury. Nature 563(7730):275-279 |
Structure of an enzyme complex essential for the metabolism of the bacterial wall of important pathogens
Structure of the essential peptidoglycan amidotransferase MurT/GatD complex from Streptococcus pneumoniae. Morlot C, Straume D, Peters K, Hegnar OA, Simon N, Villard AM, Contreras-Martel C, Leisico F, Breukink E, Gravier-Pelletier C, Le Corre L, Vollmer W, Pietrancosta N, Håvarstein LS, Zapun A. Nature Communcations ;9(1):3180 |
Structural investigation of a chaperonin in action
Structural Investigation of a Chaperonin in Action Reveals How Nucleotide Binding Regulates the Functional Cycle. Mas G, Guan J-Y, Crublet E, Colas Debled E, Moriscot C, Gans P, Schoehn G, Macek P, Schanda P, Boisbouvier J. Science Advances 2018 September 19 |
Geochemical Continuity and Catalyst/Cofactor Replacement in the Emergence and Evolution of Life
Geochemical Continuity and Catalyst/Cofactor Replacement in the Emergence and Evolution of Life. Fontecilla-Camps JC. Angewandte Chemie International Edition. doi : 10.1002/anie.201808438 |
ERC Starting Grant 2018 for Sigrid MillesThe European Research Council (ERC) has awarded a "Starting Grant" to Sigrid Milles, ‘flexibility and dynamics of proteins’ group at the IBS, to study intrinsically disordered proteins in endocytosis by single molecule fluorescence and nuclear magnetic resonance spectroscopy.
After a PhD on single molecule fluorescence spectroscopy at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany (2013), Sigrid Milles joined Martin Blackledge’s group at the IBS for a postdoc in nuclear magnetic resonance (NMR) spectroscopy. During her thesis and postdoctoral studies, Sigrid studied intrinsically disordered proteins, that means proteins without a stable three-dimensional structure. She was first interested in the proteins of the nuclear pore complex, a transport channel that connects the nucleoplasm and the cytoplasm, and her work has allowed to understand how transport through the pore can at the same time be fast (milliseconds) and specific (published in Cell, 2015). More recently, Sigrid worked on the intrinsically disordered proteins of the measles virus replication machinery and she has just discovered a new interaction site between two viral proteins (published in Science Advances, 2018), which might present a new future target to treat measles infection. She got recruited by the CNRS in 2017 and aims now to combine fluorescence and NMR spectroscopy to study the intrinsically disordered proteins in endocytosis – the major transport pathway into the eukaryotic cell. What is this project about ? Keywords : Single molecule fluorescence, nuclear magnetic resonance, intrinsically disordered proteins, endocytosis Amount of the award : €1.599 million for five years |
First results published from the European XFEL
X-ray free-electron lasers (XFELs) are novel X-ray sources that provide femtosecond pulses of a peak brilliance that exceeds that of synchrotron sources by nine orders of magnitude. The short duration of the pulses matches the chemical time scale of femtoseconds, allowing the investigation of the dynamics of matter in a time-resolved manner and enables the analysis of highly radiation-sensitive objects. IBS researchers participated in one of the first experiments at the newly built European XFEL in Hamburg, Germany, lead by the Max Planck Institute (MPI) for Medical Research in Heidelberg. This large-scale facility is the first producing XFEL pulses with a MHz repetition rate, to be compared with the 60 and 120 Hz rate of the XFELs at SACLA (Japan) and the LCLS (USA), respectively. Megahertz data collection from protein microcrystals at an X-ray free-electron laser. Grünbein ML, Bielecki J, Gorel A, Stricker M, Bean R, Cammarata M, Dörner K, Fröhlich L, Hartmann E, Hauf S, Hilpert M, Kim Y, Kloos M, Letrun R, Messerschmidt M, Mills G, Nass Kovacs G, Ramilli M, Roome CM, Sato T, Scholz M, Sliwa M, Sztuk-Dambietz J, Weik M, Weinhausen B, Al-Qudami N, Boukhelef D, Brockhauser S, Ehsan W, Emons M, Esenov S, Fangohr H, Kaukher A, Kluyver T, Lederer M, Maia L, Manetti M, Michelat T, Münnich A, Pallas F, Palmer G, Previtali G, Raab N, Silenzi A, Szuba J, Venkatesan S, Wrona K, Zhu J, Doak RB, Shoeman RL, Foucar L, Colletier JP, Mancuso AP, Barends TRM, Stan CA, Schlichting I. Nature Communications ; volume 9 : 3487 |
Revealing molecular mechanisms that prevent measles virus replication
An ultra-weak interaction in the intrinsically disordered replication machinery is essential for Measles virus function. S. Milles, M. R. Jensen, C. Lazert, S. Guseva, S. Ivashchenko, G. Communie, D. Maurin, D. Gerlier, R. W. H. Ruigrok, M. Blackledge. Sci. Adv. 4, eaat7778 |
A modified Fe-S cluster modulates [Ni-Fe] hydrogenase oxidative damage
X-ray structural, functional and computational studies of the O2-sensitive E. coli hydrogenase-1 C19G variant reveal an unusual [4Fe–4S] cluster. A. Volbeda, J. M. Mouesca, C. Darnault, M. M. Roessler, A. Parkin, F. A. Armstrong and J. C. Fontecilla-Camps. ChemComm ; accepted 4th June 2018, DOI : 10.1039/c8cc02896f |
C1q and MBL opsonins use a common anchor site on the CR1 receptor
C1q and MBL interact with CR1 in the same region on CCP24-25 modules. Jacquet M, Cioci G, Fouët G, Bally I, Thielens NM, Gaboriaud C, Rossi V. Frontiers in Immunology ;9, 453 |
How Detergent Impacts Membrane Proteins
1) How Detergent Impacts Membrane Proteins : Atomic-Level Views of Mitochondrial Carriers in Dodecylphosphocholine. Kurauskas V, Hessel A, Ma P, Lunetti P, Weinhäupl K, Imbert L, Brutscher B, King MS, Sounier R4, Dolce V, Kunji ERS, Capobianco L, Chipot C, Dehez F, Bersch B, Schanda P. Journal of Physical Chemistry Letters ;9(5):933-938 |
New light on the mevalonate bioynthetic reaction in archaeaMevalonate is a starting material to synthesize many chemicals in industry ; it is also the building block of the lipids from all archaea. Scientists at the IBS and and collaborators at the Max Planck Institute for Terrestrial Microbiology in Marburg and ENS Lyon discovered a coupling between the two enzymes responsible for the first step in mevalonate biosynthesis in archaea. This finding explain how archaea can produce mevalonate at high rate to support their growth, and can be applied in industry to optimize mevalonate production. Details Archaeal acetoacetyl-CoA thiolase/HMG-CoA synthase complex channels the intermediate via a fused CoA-binding site. Vögeli, B., Engilberge, S., Girard, E., Riobé, F., Maury, O., Erb, T.J., Shima, S., Wagner, T. PNAS, 115(13) : 3380-3385 |
Deciphering the Dynamic Interaction Profile of an Intrinsically Disordered Protein by NMR Exchange Spectroscopy
Deciphering the Dynamic Interaction Profile of an Intrinsically Disordered Protein by NMR Exchange Spectroscopy. Delaforge E, Kragelj J, Tengo L, Palencia A, Milles S, Bouvignies G, Salvi N, Blackledge M, Jensen MR. Journal of the American Chemical Society ;140(3):1148-1158 |
Capture of a « phantom » state of green fluorescent proteins
A Long-Lived Triplet State Is the Entrance Gateway to Oxidative Photochemistry in Green Fluorescent Proteins. Byrdin M, Duan C, Bourgeois D, Brettel K. Journal of the American Chemical Society ;. doi : 10.1021/jacs.7b12755 |
How bacteria converse in floating biofilms
Porin self-association enables cell-to-cell contact in Providencia stuartii floating communities. El-Khatib M, Nasrallah C, Lopes J, Tran QT, Tetreau G, Basbous H, Fenel D, Gallet B, Lethier M, Bolla JM, Pagès JM, Vivaudou M, Weik M, Winterhalter M, Colletier JP. Proceedings of the National Academy of Sciences of the United States of America. 2018 Feb 23. pii : 201714582. doi : 10.1073/pnas.1714582115. |
Bacterial pathogens can reprogram target cells by influencing epigenetic factors
Pore-forming activity of the Pseudomonas aeruginosa type III secretion system translocon alters the host epigenome. Laurent Dortet, Charlotte Lombardi, François Cretin, Andréa Dessen, Alain Filloux. Nature Microbiology 2018 Feb 5. doi : 10.1038/s41564-018-0109-7 |
Analytical Description of NMR Relaxation Highlights Correlated Dynamics in Intrinsically Disordered Proteins
Analytical Description of NMR Relaxation Highlights Correlated Dynamics in Intrinsically Disordered Proteins. Salvi N, Abyzov A, Blackledge M. Angewandte Chemie International Edition England ;56(45):14020-14024. |
Antibiotics and radical-based chemistry : the 1,2-diol dehydratase AprD4 from the inside
1,2-diol dehydration by the radical SAM enzyme AprD4 - a matter of proton circulation and substrate flexibility. Liu WQ, Amara P, Mouesca JM, Ji X, Renoux O, Martin L, Zhang C, Zhang Q, Nicolet Y. Journal of the American Chemical Society 2018 Jan 4. doi : 10.1021/jacs.7b10501. [Epub ahead of print] |