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Solid State NMR Maps Functional Protein Dynamics Inside the Crystal
Over the last 8 years the IBS (FDP group) and the ENS Lyon (Centre Européen de RMN) have combined their complementary expertise to develop pioneering studies of protein dynamics in the solid state. The potential applications of this novel methodology (very large molecular assemblies, amyloid aggregates, membrane proteins…) underline the importance of these unique studies for the development of a general understanding of the role of protein dynamics in biological processes. Since the first ever measurements of site-specific 15N relaxation rates in 2004 [1] this successful collaboration has progressively addressed and resolved fundamental experimental and analytical challenges, and is now poised to develop a unified description of protein dynamics from solution to the solid state. The most recent milestones resulting from this collaboration describe the first ever experimental characterisation of collective modes of motion in microcrystalline proteins by NMR [2], the measurement of site specific 13C relaxation rates [3] and most recently, the measurement of atomic-resolution slow motions in the micro-millisecond range [4] This ongoing project has been generously and continuously supported by the ANR, the European Union and the French Ministry of Research. 1) Site-specific backbone dynamics from a crystalline protein by solid-state NMR spectroscopy. N. Giraud, A. Böckmann, A. Lesage, F. Penin, M. Blackledge, L. Emsley. J.Am.Chem.Soc. 126, 11422-11423, (2004). |
Molecular basis for amyloid-{beta} polymorphism
Molecular basis for amyloid-beta polymorphism. |
A student of IBS selected for the iGEM contest, a competition of synthetic biology from MIT (United States)Marion Cristea, a 2nd year student at Phelma and an IBS traineeship (under the joint supervision of T. Vernet - Pneumococcus group) was part of the Grenoble team qualified to participate iGEM 2011 World The International Genetically Engineered Machine competition (iGEM) is the premiere undergraduate Synthetic Biology competition. In 2011 this event brings together 166 teams from over 50 countries and coming from the best universities and schools in the world (MIT, Harvard, Cambridge ...). Student teams are given a kit of biological parts and they shall use these parts and new parts of their own design to build biological systems and operate them in living cells. The Grenoble team was qualified for the final hold in Boston, USA from November 5-7. They presented a unique bacterium that can detect mercury in water. Learn more about their project : |
Shedding new light on fluorescent proteins’ dark states
The Nature of Transient Dark States in a Photoactivatable Fluorescent Protein. Arijit Roy, Martin J. Field, Virgile Adam and Dominique Bourgeois. JACS ;133(46):18586-9 |
20th Anniversary of Science Festival at the IBSFor the 20th anniversary of the French Science week, the IBS invited high school students and primary school pupils to discover the daily life of researchers, the different jobs offered in a research institute and the interest of a thorough knowledge of proteins. A general presentation and three workshops (RMN, Cristallography and Biochemistry) were proposed to125 high school students.
To develop children’s curiosity for science the IBS staff organized science experiments for a hundred pupils involving proteins and DNA. After these short experiments children were invited to visit a laboratory.
More than thirty volunteers were mobilized for this event, now eight years old at the IBS. |
Foundation stone of the new building laid by French Minister of Science and Higher EducationOn October 6, Laurent Wauquiez, French Minister for Science and Higher Education, laid the foundation stone of the new IBS building. He was accompanied by the Mayor of Grenoble, Michel Destot, the Deputy Mayor, Geneviève Fioraso, the General administrator of the CEA, Bernard Bigot, and the President of the University Joseph Fourier-Grenoble 1, Farid Ouabdesselam.
After meeting with IBS group leaders , the ceremony began with a dynamic introduction by Eva Pebay-Peyroula, Director of the IBS. Farid Ouabdesselam spoke on behalf of the IBS operating organizations (CEA-CNRS-UJF), followed by speeches by the funding partners. The Minister underlined the excellent scientific potential of the region and the important role played by researchers in Society. A plaque in honor of the Minister will be placed in the new building. The construction of this IBS building on the EPN Campus is part of the Giant-Innovation Campus development project. It is funded by the Campus Plan and the state/regional granting agency CPER with major contributions from Regional and Local Governments (Metro, City of Grenoble, General Council). This new location, close to the EMBL, ESRF and ILL, will bring together an outstanding range of expertise and facilities in life science and provide a unique environment for state-of-the-art integrated structural biology in Europe. |
Subfunctionalization of a chemokine (CXCL12) through altered interaction with the receptorCXCL12, a member of the chemokine family, promotes directional migration of cells within tissues. In zebrafish embryos, two distinct CXCL12 paralogs are expressed suggesting a mechanism through which migrating cells prioritize the relevant cues they encounter. In a paper published in “Development”, Erez Raz et coll. show that primordial germ cells respond preferentially to one of the paralogs and demonstrate that a single amino acid change (N33S) switches the relative affinity of the CXCL12 ligands towards one of the duplicated CXCR4 receptors. In collaboration with this team, the SAGAG group showed that the N/S change did not induce any modification in the structure nor the ability of the chemokine to bind heparan sulphate, therefore demonstrating that the functional specialization of each paralog to elicit complementary functions is based on the receptor-ligand interaction rather than the biochemical features of the protein. Control of CXCL12 function by ligand subfunctionalization. Boldajipour B., Doitsidou M., Tarbashevich K., Laguri C., Yu S.R., Ries J., Dumstrei K., Thelen S., Dörries J., Messerschmidt E-M., Thelen M., Schwille P., Brand M., Lortat-Jacob H., Raz E. Development 138, 2909-2914 |
Nano-particles on duty of health
Softness of Atherogenic Lipoproteins : A Comparison of Very Low Density Lipoprotein (VLDL) and Low Density Lipoprotein (LDL) Using Elastic Incoherent Neutron Scattering (EINS). Mikl, C., Peters, J., Trapp, M., Kornmueller, K., Schneider, W. and Prassl, R. Journal of the American Chemical Society 133 (2011), 13213 - 13215 . |
Detailed insight into protein side chain motion from solid-state NMR spectroscopy
Solid-State NMR Measurements of Asymmetric Dipolar Couplings provide Insight into Protein Side-Chain Motion. Schanda P, Huber M, Boisbouvier J, Meier BH, Ernst M. Angew Chem Int Ed Engl. ; 50(46):11005-9 |
A fluorescent protein for cryo-nanoscopy
Low-temperature chromophore isomerization reveals the photoswitching mechanism of the fluorescent protein Padron. Regis-Faro, Aline ; Carpentier, Philippe ; Jonasson, Gabriella ; Pompidor, Guillaume ; Arcizet, Delphine ; Demachy, Isabelle ; Bourgeois, Dominique. |
An innovative technology for pathogens detectionPrestodiag is a project led by researchers at the Institut nanosciences et cryogénie (INAC) and the Institut de Biologie Structurale (IBS). It offers innovative technology to monitor in real time the growth of pathogenic bacteria present in a complex sample. Analysis of samples for the detection of pathogens responsible for infections is a tedious time consuming and highly operator-dependent process. Conduct these tests takes 1 to 7 days because they require a long period to grow bacteria and an expensive equipment. The Prestodiag project proposes to develop a technique that dramatically reduces the duration of the analysis and allows direct measurement of small amounts of bacteria in samples, like food. The purpose of Prestodiag is to develop, produce and commercialize compact, fast, reliable and robust diagnostic devices for the detection of bacteria in different fluids (water, milk, urine ...), for the food industry or the medical sector. The project is lead by Thibaut Mercey (INAC) and supported by the CEA. In 2011, it was awarded in a competition supporting the creation of startup companies with innovative technological products, in the "emerging technologies" category. The technology involved was developed by Thierry Livache and his team (INAC/ SPrAM), and Thierry Vernet and Claire Durmort (IBS/Pneumococcus Group). Contacts : |
Amphipols, from chemistry to biologyThese amphiphilic polymers designed by J.-L Popot (Paris) can substitute for detergents to keep integral membrane proteins water soluble with generally greatly improved biochemical stability. The review discusses their structure and solution behaviour, the way they associate with membrane proteins - investigated in part at IBS - and their applications. Amphipols from a to z* ; Popot, J.-L., Althoff, T., Bagnard, D., Baneres, J. L., Bazzacco, P., Billon-Denis, E., Catoire, L. J., Champeil, P., Charvolin, D., Cocco, M. J., Cremel, G., Dahmane, T., de la Maza, L. M., Ebel, C., Gabel, F., Giusti, F., Gohon, Y., Goormaghtigh, E., Guittet, E., Kleinschmidt, J. H., Kuhlbrandt, W., Le Bon, C., Martinez, K. L., Picard, M., Pucci, B., Sachs, J. N., Tribet, C., van Heijenoort, C., Wien, F., Zito, F., and Zoonens, M. |
6th IBS scientific dayThe sixth IBS scientific day was held on June 21, 2011 at St Hugues de Biviers. The format of the event included conferences on each research themes and flashs & poster presentations by PhD students and post-docs. The poster price was awarded to Romain Talon. This event was an opportunity for all the staff to gather in an attractive setting for a scientific and festive moment.
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DNA repair inspires photoreception
The cryptochromes : Blue light photoreceptors in plants and animals. |
A new approach to investigate protein-glycosaminoglycan complexesIBS Researchers (SAGAG and NMR groups), in collaboration with their colleagues of the CERMAV-Grenoble, developed a novel approach to structurally investigate protein-glycosaminoglycan complexes. This method is based on the production of 13C-labeled heparan sulphate by E. coli-K5 fermentation and chemical modifications, which in combination with a 15N-labeled protein, can be analysed by multidimensional NMR spectroscopy.
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Intrinsic disorder in measles virus nucleocapsids
Intrinsic disorder in measles virus nucleocapsids. Malene Ringkjøbing Jensen, Guillaume Communie, Euripedes Almeida Ribeiro Jr, Nicolas Martinez, Ambroise Desfosses, Loïc Salmon, Luca Mollica, Frank Gabel, Marc Jamin, Sonia Longhi, Rob W. H. Ruigrok, and Martin Blackledge. PNAS ;108(24):9839-44. |
Investing in the Future : the IBS as partner in two national calls
In July 2010, the French government launched a new initiative aiming to give the country a strong research infrastructure that would allow the nation’s researchers to be highly competitive on the international stage.The IBS is partner in two projects. The IBS as founding partner within the Laboratories of Excellence initiative (Labex) The GRAL project has been selected among 241 projects for funding in response to the Labex call (Laboratories of Excellence initiative). GRAL, (Alliance grenobloise pour la biologie structurale et cellulaire intégrées), brings together three life science institutes in Grenoble with the aim to achieve convergence between structural and integrative cell biology in the context of two research areas : host-pathogens interactions and the chloroplast as a model organelle. The IBS as partner in a national infrastructure initiative Of the 37 scientific projects submitted for consideration in the national infrastructure initiative, nine were awarded funding by the program. One of these, a project called FRISBI, involves the structural biology community of Grenoble, in particular the IBS and the UVHCI. |
Carbon nanotubes attract and organize human proteins of the complement system without activating it
Proteins of the innate immune system crystallize on carbon nanotubes but are not activated. Ling WL, Biro A, Bally I, Tacnet P, Deniaud A, Doris E, Frachet P, Schoehn G, Pebay-Peyroula E and Arlaud GJ. ACS Nano ;5(2):730-737. |
What is flipping the glycolipopeptide essential for bacterial life ?The cell wall of bacteria guarantees the cell integrity and acts as an active filter towards the extracellular environment. Synthesis of the main essential constituent of the wall, peptidoglycan (PG), is inhibited by antibiotics like penicillin. PG is a polymer assembled on the bacteria surface by enzymes from the precursor Lipid II : a long lipid chain linked to a two-sugars moiety itself decorated by a 5-amino acid long peptide. This glycolipopeptide is synthesized inside the bacteria and, until now, the mechanism allowing Lipid II to reach the bacterial surface assembly site was unknown. In collaboration with the group headed by Eefjan Breukink in the Netherlands, we have identified FtsW as the transporter of Lipid II across the plasma membrane. FtsW is an essential protein required for the division and establishment of the shape of all bacteria. It is an integral membrane protein whose challenging recombinant production and purification was used to demonstrate its activity in flipping Lipid II across bacterial membrane vesicles as well as a in model membranes in vitro. Our current efforts at the IBS aim at reconstituting and characterizing the membrane protein complexes encompassing FtsW responsible for the various phases of division and morphogenesis in the pneumococcus. Knowledge derived form this work is fully relevant for the discovery of new means of inhibiting bacterial growth, in other words for the development of novel antibiotics. Identification of FtsW as a transporter of lipid-linked cell wall precursors across the membrane. Mohammadi T., et al. EMBO J. ;30(8):1425-32 |
Structure, Dynamics and Kinetics of Ultra-weak Protein Complexes by NMR
Structure, dynamics, and kinetics of weak protein-protein complexes from NMR spin relaxation measurements of titrated solutions. |
High resolution NMR structure of ribonucleic acid enzyme reveals insight into the formation of the active siteIn a collaboration with Pr. Pascale Legault from Biochemistry Department of University of Montreal, Jerome Boisbouvier (Biomolecular NMR Spectroscopy Group of IBS) has contributed to the structural investigation at atomic resolution of an domain of Neurospora VS ribozyme using liquid crystal NMR technology. This high resolution NMR structures of the A730 loop and the active conformation of the SLI internal loop, were used to model the active site of the VS ribozyme. NMR structure of the A730 loop of the Neurospora VS ribozyme : insights into the formation of the active site. Desjardins G, Bonneau E, Girard N, Boisbouvier J and Legault P. Nucleic Acids Research ;39(10):4427-37 |
Investing in the Future : the IBS as partner in a national infrastructure initiativeIn July 2010, the French government launched a new initiative aiming to give the country a strong research infrastructure that would allow the nation’s researchers to be highly competitive on the international stage. Of the 37 scientific projects submitted for consideration, nine were awarded funding by the program. One of these, a project called FRISBI, involves the structural biology community of Grenoble, in particular the IBS and the UVHCI. FRISBI was awarded five years of funding worth a total of 32 M€, which will be distributed among 5 partner sites (Strasbourg, Grenoble, Marseille, Montpellier and Paris-Sud). The project will allow for the seamless integration of structural biological data obtained using different in vitro and in vivo techniques. This approach will ultimately advance our understanding of how proteins, macromolecular complexes, and pathogenic agents such as viruses and bacteria interact with their cellular environment. |
New electron microscope at the IBSOne of the latest generation of electron microscopes was inaugurated at the IBS on February 11, 2011, in presence of the funding bodies and Guillaume Lissy, representing the President of the Rhône-Alpes Region. This FEI Tecnai Polara microscope, the second of its kind in France, will allow scientists to :
This microscope is unique in the south of France, and will be open to the entire scientific community. It will enable the local scientists to remain globally competitive and help in their quest to make promising discoveries related to human diseases. A mini-symposium by experts of cryomicroscopy and tomography concluded this event :
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A new bacterial strategy to control immunity
A Bacterial Protein Targets the BAHD1 Chromatin Complex to Stimulate Type III Interferon Response. Alice Lebreton, Goran Lakisic, Viviana Job, Lauriane Fritsch, To Nam Tham, Ana Camejo, Pierre-Jean Matteï, Béatrice Regnault, Marie-Anne Nahori, Didier Cabanes, Alexis Gautreau, Slimane Ait-Si-Ali, Andréa Dessen, Pascale Cossart, and Hélène Bierne. Science, 331 : 1319-1321. |