Accueil > Research > Highlights > Archives > 2019
A Unified Description of Intrinsically Disordered Protein Dynamics under Physiological Conditions using NMR Spectroscopy
A Unified Description of Intrinsically Disordered Protein Dynamics under Physiological Conditions using NMR Spectroscopy. Wiktor Adamski, Nicola Salvi, Damien Maurin, Justine Magnat, Sigrid Milles, Malene Ringkjøbing Jensen, Anton Abyzov, Christophe Moreau, Martin Blackledge. Journal of the American Chemical Society ; 141(44):17817-17829 |
Structural basis for broad HIV-1 neutralization by the MPER-specific human Broadly neutralizing antibody LN01
Structural basis for broad HIV-1 neutralization by the MPER-specific human Broadly neutralizing antibody LN01. Pinto D, Fenwick C, Caillat C, Silacci C, Guseva S, Dehez F, Chipot C, Barbieri S, Minola A, Jarrossay D, Tomaras GD, Shen X, Riva A, Tarkowski M, Schwartz O, Bruel T, Dufloo J, Seaman MS, Montefiori DC, Lanzavecchia A, Corti D, Pantaleo G and Weissenhorn W. Cell Host Microbe ; 26(5):623-637.e8. |
Paoletti Prize 2019 for Sigrid Milles (IBS/FDP)
|
Official opening of the 2019 Science Festival in Isere on EPN CampusThursday 03 October saw the official opening of the 2019 Science Festival on the EPN Campus. The launching of the 2019 Science Festival in Isere began with visits of the NMR and electron microscopy platforms of the IBS, the ESRF tunnel, the EMBL-IBS partnership platform for high throughput protein crystallography, the Science building and two ILL-ESRF joint laboratories were proposed. Then the opening ceremony in the IBS seminar room was attended by Chloé Lombard, representing Mr Préfet de l’Isère, Viviane Henry, representing Madam Rector of the Academy of Grenoble, Christophe Ferrari, the President of Grenoble Alpes Metropole, Eric Piolle, Mayor of Grenoble, and Jeany Jean-Baptiste, Director of la Casemate. The directors of the four EPN institutions (EMBL, ESRF, IBS, ILL) and people in charge of the Science Festival in other academic laboratoires or associations were also present.
It was a great opportunity to highlight our cooperative research facilities and our commitment to the promotion and dissemination of science. |
A chimeric pseudo-adenovirus to combat emergent diseases
Synthetic self-assembling ADDomer platform for highly efficient vaccination by genetically encoded multiepitope display. Charles Vragniau, Joshua C. Bufton, Frédéric Garzoni, Emilie Stermann, Fruzsina Rabi,Céline Terrat, Mélanie Guidetti, Véronique Josserand, Matt Williams, Christopher J. Woods, Gerardo Viedma, Phil Bates, Bernard Verrier, Laurence Chaperot, Christiane Schaffitzel, Imre Berger and Pascal Fender. Science Advances ; Vol. 5, no. 9, eaaw2853 |
Integrated NMR and cryo-EM atomic-resolution structure determination of a half-megadalton enzyme complex
Integrated NMR and cryo-EM atomic-resolution structure determination of a half-megadalton enzyme complex. Gauto DF, Estrozi LF, Schwieters CD, Effantin G, Macek P, Sounier R, Sivertsen AC, Schmidt E, Kerfah R, Mas G, Colletier JP, Güntert P, Favier A, Schoehn G, Schanda P, Boisbouvier J. Nature Communications ;10(1):2697 |
Insights into the movements of aromatic residues in a 0.5 MDa enzyme by solid-state NMR
Aromatic Ring Dynamics, Thermal Activation, and Transient Conformations of a 468 kDa Enzyme by Specific 1H-13C Labeling and Fast Magic-Angle Spinning NMR. Gauto DF, Macek P, Barducci A, Fraga H, Hessel A, Terauchi T, Gajan D, Miyanoiri Y, Boisbouvier J, Lichtenecker R, Kainosho M, Schanda P. Journal of the American Chemical Society ; 141(28):11183-11195 |
Mechanism of allosteric activation of an enzyme by an inhibitor
Mechanism of the allosteric activation of the ClpP protease machinery by substrates and active-site inhibitors. Felix J, Weinhäupl K, Chipot C, Dehez F, Hessel A, Gauto DF, Morlot C, Abian O, Gutsche I, Velazquez-Campoy A, Schanda P, Fraga H. Science Advances ; Vol. 5, no. 9, eaaw3818 |
Cell morphology and nucleoid dynamics in dividing D. radiodurans.
Cell morphology and nucleoid dynamics in dividing D. radiodurans. Floc’h K, Lacroix F, Servant P, Wong YS, Kleman JP, Bourgeois D and Timmins. Nature Communications ; 10(1):3815 |
3.3 Å resolution structure of Hantaan virus nucleocapsid revealed by cryo-EM
High resolution cryo-EM structure of the helical RNA-bound Hantaan virus nucleocapsid reveals its assembly mechanisms. Arragain B, Reguera J, Desfosses A, Gutsche I, Schoehn G, Malet H. Elife ; 8. pii : e43075. |
Importance of lncRNA tertiary structure in key cellular processes
Conserved pseudoknots in lncRNA MEG3 are essential for stimulation of the p53 pathway. Uroda T, Anastasakou E, Rossi A, Teulon J-M, Pellequer J-L, Annibale P, Pessey O, Inga A, Chillon I and Marcia M. Mol. Cell 75 : 1-14. |
A strategy to reduce fluorescence intermittencies in sptPALM
Mechanistic investigation of mEos4b reveals a strategy to reduce track interruptions in sptPALM. De Zitter E, Thédié D, Mönkemöller V, Hugelier S, Beaudouin J, Adam V, Byrdin M, Van Meervelt L, Dedecker P and Bourgeois D. Nature Methods ; volume 16, pages707–710. |
Mechanism for assembling pores on the bacterial surface : a strategy for secreting toxins
Structure and assembly of pilotin-dependent and -independent secretins of the Type II secretion system. Howard SP, Estrozi L, Contreras-Martel C, Bertrand Q, Job V, Martins A, Schoehn G, Dessen A. PLoS Pathogens ; 15(5):e1007731 |
Double labelling to facilitate the study of glycosaminoglycans
In this context, the researchers of the SAGAGAG group, in collaboration with the Parisian Institute of Molecular Chemistry and the LG2A laboratory in Amiens, have developed a method allowing a double labelling of HS oligosaccharides, using Thia-Michael type addition and deuterium incorporation, respectively at the non-reducing and reducing ends of the sugar. This new labelling technique allows the combination of microgram-scale oligosaccharide labelling and mass spectrometric analysis, without altering HS/protein recognition properties, as demonstrated for heparinase I and HSulf-2 enzymes. This method is a new tool that should allow new developments for the sequencing of GAG oligosaccharides and the elucidation of new structure/function relationships. A microscale double labelling of GAG oligosaccharides compatible with enzymatic treatment and mass spectrometry. Przybylski C, Bonnet V, Vivès RR. Chemical Communications ; 55(29):4182-4185. |
Targeting host proteins to fight influenza
Destabilization of the human RED–SMU1 splicing complex as a basis for host-directed antiinfluenza strategy. Ashraf U, Tengo L, Le Corre L, Fournier G, Busca P, McCarthy AA, Rameix-Welti M-A, Gravier-Pelletiere C, Ruigrok RW, Jacob Y, Vidalain P-O, Pietrancosta N, Crépin T, Naffakh N. Proc Natl Acad Sci USA ;116(22):10968-10977. |
How viruses release from cells after infecting them
VPS4 triggers constriction and cleavage of ESCRT-III helical filaments. Maity S, Caillat C, Miguet N, Sulbaran G, Effantin G, Schoehn G, Roos WH, Weissenhorn W. Science Advances ;5(4):eaau7198 |
ERC Advanced Grant 2019 for Martin Blackledge
Martin Blackledge is FDP group leader and Deputy Director at the IBS in Grenoble. His project entitled "DynamicAssemblies" will receive € 2.5 million financial support from the ERC over 5 years. Scientific excellence at European level is one of the main criteria for the selection of these awards dedicated to ground-breaking, high-risk projects presented by active leading Principal Investigators with a track-record of significant research achievements in the last 10 years. Martin Blackledge studied physics at the University of Manchester and received his doctorate (D. Phil) in 1987 under the direction of Professor George Radda at the University of Oxford developing techniques for biomolecular NMR spectroscopy in vivo. In 1989 he received a Royal Society Fellowship to work at the ETH Zürich under the supervision of Professor Richard Ernst (Nobel prize for chemistry 1991) where he first started to develop methods to study biomolecular dynamics by NMR. Having discovered the beauty of the Alps, he decided to continue this work at the Institut de Biologie Structurale (CEA/CNRS/UGA) in Grenoble where he has headed the “Protein Dynamics and Flexibility by NMR” group since 2007. The primary research interest of the Blackledge group is the study of protein dynamics by NMR, often combined with complementary biophysical techniques and advanced molecular simulation, to characterize the role of conformational flexibility in biological function on a broad range of time and length scales, from molecular recognition dynamics in folded proteins, to reorganizational dynamics of large multi-domain assemblies exhibiting extensive protein disorder to the study of fundamental physics underlying protein dynamics. He has published over 200 articles in this field. Most recently his group uses these techniques to describe highly flexible or intrinsically disordered proteins (IDPs), to map the thermodynamics and kinetics of their interaction trajectories at atomic resolution, and to determine the relationship between their dynamic behaviour and functional mechanism. What is this project "DynamicAssemblies" about ? IDPs are present throughout all known proteomes, playing important roles in functional mechanisms in all aspects of biology. Many molecular assemblies comprise highly dynamic components that are functionally essential. The elaboration of time-resolved, atomic resolution descriptions of the interaction trajectories of such highly disordered complexes, comprising both folded and disordered domains, is extremely challenging, requiring the development of adapted methodologies that can account for their intrinsic flexibility. Keywords Amount of the award |
High resolution structure determination of measles nucleocapsides
(1) Self-assembly of measles virus nucleocapsid-like particles : Kinetics and RNA sequence dependence. Milles, Jensen, Communie, Maurin, Schoehn, Ruigrok, Blackledge. Angew Chem Int Ed 55, 9356 (2016) (2) Assembly and cryo-EM structures of RNA-specific measles virus nucleocapsids provide mechanistic insight into paramyxoviral replication. Desfosses A, Milles S, Jensen MR, Guseva S, Colletier JP, Maurin D, Schoehn G, Gutsche I, Ruigrok RWH, Blackledge M. Proc Natl Acad Sci U S A. ; doi : 10.1073/pnas.1816417116. |
Algal Remodeling in a Ubiquitous Planktonic Photosymbiosis
The IBS-ISBG electron microscopy platform was involved in the preparation of the planctonic or cultured samples for electron microscopy imaging. An optimized sample preparation was also set up for correlative imaging between structural (TEM, SEM, FIB-SEM) and chemical imaging (X-ray fluorescence microscopy, SIMS). Algal Remodeling in a Ubiquitous Planktonic Photosymbiosis. Decelle J, Stryhanyuk H, Gallet B, Veronesi G, Schmidt M, Balzano S, Marro S, Uwizeye C, Jouneau PH, Lupette J, Jouhet J, Maréchal E, Schwab Y, Schieber NL, Tucoulou R, Richnow H, Finazzi G, Musat N. Current Biology ; doi : 10.1016/j.cub.2019.01.073 |
Molecular decoding of a key step in the maturation process of heparan sulfate
Substrate binding mode and catalytic mechanism of human heparan sulfate D-glucuronyl C5 epimerase. Debarnot C, Monneau Y R, Roig-Zamboni V, Delauzun V, Le Narvor C, Richard E, Hénault J, Goulet A, Fadel F, Vivès R R, Priem B, Bonnaffé D, Lortat-Jacob H, Bourne Y. Proc Natl Acad Sci USA published ahead of print March 14, 2019 https://doi.org/10.1073/pnas.1818333116 |
Cellular binding of a virus developed in cancer therapy elucidated at the atomic levelAdenoviruses cause diseases that can sometimes be fatal. By modifying them, they can also become formidable cancer cell killers. Adenoviruses are to date the most commonly used vectors in human clinical trials. Researchers have just elucidated by cryo electron microscopy the mechanism by which adenoviruses attach themselves to the cell surface. These results, published in the journal Nature Communication on March 12, 2019, could pave the way for the development of new generation anti-tumor vectors.
Cryo-EM structure of adenovirus type 3 fibre with desmoglein 2 shows an unsual mode of receptor engagement. Vassal-Stermann E, Effantin G, Zubieta C, Burmeister W, Iséni F, Wang H, Lieber A, Schoehn G, Fender P. Nature Communications in press, (2019) |
How much one electron can do
The Crystal Structure of the Transcription Regulator RsrR Reveals a [2Fe-2S] Cluster Coordinated by Cys, Glu and His Residues. Volbeda A, Pellicer Martinez MT, Crack JC, Amara P, Gigarel O, Munnoch JT, Hutchings MI, Darnault C, Le Brun NE, Fontecilla-Camps JC. J Am Chem Soc. 2019 Jan 18. doi : 10.1021/jacs.8b10823. |
New insights into the recognition mechanisms of Heparan sulfate by SULF sulfatases
Expression and purification of recombinant extracellular sulfatase HSulf-2 allows deciphering of enzyme sub-domain coordinated role for the binding and 6-O-desulfation of heparan sulfate. Seffouh A, El Masri R, Makshakova O, Gout E, Hassoun ZEO, Andrieu JP, Lortat-Jacob H, Vivès RR. Cell. Mol. Life Sci. (2019).https://doi.org/10.{{1007/s00018-019-03027-2 |
A new Cryo-electron microscope for the IBS
Contacts : G. Schoehn and E. Neumann for the ISBG/IBS Cryo-electron microscopy platform, ibs-plateforme-em.contact@ibs.fr. |