Institut de Biologie StructuraleGrenoble / France


Using super‐slow motion movie, scientists pin down the workings of a key proton pump

Using powerful new tools, scientists from the RIKEN SPring-8 Center and collaborators from Sweden, Switzerland, Germany and France, including Antoine Royant researcher from the IBS, have demonstrated how bacteriorhodopsin, a "proton pump", uses light to transport protons across the cell membrane to create a charge difference that can be used to power a cell’s activities.
Antoine Royant, researcher of the Synchrotron group at the IBS, contributed to the structural analysis of the 13 structures of intermediate states obtained over 5 orders of magnitude of time scale and to the identification of the mechanism of the protein.
This result was published in Science on December 23, 2016. Details

A three-dimensional movie of structural changes in bacteriorhodopsin. Nango E, Royant A, Kubo M, Nakane T, Wickstrand C, Kimura T, Tanaka T, Tono K, Song C, Tanaka R, Arima T, Yamashita A, Kobayashi J, Hosaka T, Mizohata E, Nogly P, Sugahara M, Nam D, Nomura T, Shimamura T, Im D, Fujiwara T, Yamanaka Y, Jeon B, Nishizawa T, Oda K, Fukuda M, Andersson R, Båth P, Dods R, Davidsson J, Matsuoka S, Kawatake S, Murata M, Nureki O, Owada S, Kameshima T, Hatsui T, Joti Y, Schertler G, Yabashi M, Bondar AN, Standfuss J, Neutze R, Iwata S. Science; 354(6319):1552-1557

The EMBL-IBS High-throughput crystallography platform inaugurated

PHOTO: ILL/Serge Claisse

A refurbished and upgraded High-Throughput Crystallography (HTX) platform has been launched on the European Photon and Neutron Science (EPN) Campus in Grenoble. The platform offers robotics for crystallisation of both soluble and membrane proteins and automated crystal harvesting thus promoting efficient structure determination by X-ray crystallography for scientists, from pharmaceutical companies and academia. The new HTX platform is a joint effort between EMBL Grenoble and the Institut de Biologie Structurale (IBS): the EMBL HTX platform offers services in crystallisation of water-soluble proteins and automated crystal harvesting and the IBS platform is specialised in crystallisation of membrane proteins.
Researchers in Europe can access the facility through funding from the EC-funded iNEXT project .
To know more

The birth of the brightest red glowing protein

The brightest red fluorescent protein ever, mScarlet, has just been engineered by researchers at the IBS, the University of Amsterdam and the European Synchrotron (ESRF). mScarlet can be used to monitor the activity in cells and replaces its predecessors with unprecedented brightness. That brightness will serve cellular microscopy well as it ensures the visibility of the proteins studied by scientists. Moreover, mScarlet is an ideal illuminating agent as it does not affect the functioning of the proteins to which it is tagged. The findings are published in Nature Methods. To know more

mScarlet: a bright monomeric red fluorescent protein for cellular imaging. Daphne S. Bindels, Lindsay Haarbosch, Laura van Weeren, Marten Postma, Katrin E. Wiese, Marieke Mastop, Sylvain Aumonier, Guillaume Gotthard, Antoine Royant, Mark A. Hink and Theodorus W.J. Gadella Jr. Nature Methods doi: 10.1038/nmeth.4074.

A protein channel connects the mother cell and forespore during sporulation

Bacterial sporulation, which is induced by nutrient starvation, is a simple model of morphological differentiation and leads to the development of a spore that is resistant to extreme environments (temperature, dehydration, irradiation, …). A key stage of the spore development cycle is the assembly of a hetero-multimeric complex, which is composed of at least 9 different proteins (SpoIIIAA-SpoIIIAH and SpoIIQ) and spans the membranes of the mother cell and forespore. Although the function of this complex remains mysterious, the similarities of the SpoIIIA proteins with components founds in flagella and type II, III and IV secretion systems suggest that it might be involved in the secretion or the passive transport of an unknown molecule from the mother cell to the forespore. The Pneumococcus, Electron Microscopy and Methods, biomolecular NMR groups at the IBS, in collaboration with the group of David Rudner at Harvard Medical School in Boston, have generated complementary data in structural and cellular biology, showing that SpoIIIAG forms an oligomeric ring required for forespore development. The 3D reconstruction of this ring using cryo-EM has revealed a "cup-and-saucer" architecture displaying a 6-nm central pore. This study provides the first direct evidence that a protein channel connects the mother cell to the forespore during sporulation.

A ring-shaped conduit connects the mother cell and forespore during sporulation in Bacillus subtilis. Rodrigues CD, Henry X, Neumann E, Kurauskas V, Bellard L, Fichou Y, Schanda P, Schoehn G, Rudner DZ, Morlot C. Proc Natl Acad Sci U S A 113(41):11585-11590.

Two peptides and six sulfates combine to block HIV entry

In a study, conducted by the SAGAG group of the IBS, researchers from the CNRS, the CEA, the Pasteur institute, the Antwerp institute of Tropical Medicine and the Grenoble-Alpes and Paris-Sud universities, describe the design, the chemical synthesis, the biochemical analysis and the anti-viral activity of an original bispecific molecule, called mCD4-PS. Consisting of a CD4 mimic peptide and a sulfopeptide mimicking heparan sulfates, this compound targets the gp120 viral envelope protein and, despite a size reduced to 5.5 kDa, simultaneously inhibits the binding sites of the viral receptor and co-receptors (CD4, CCR5 and CXCR4) with sub nM IC50. A preclinical study, performed using a macaque model of vaginal infection shows that this molecule has protected 83% of the treated animals. As a result of these encouraging results, a second-generation of molecules have been designed which show ten times more active anti-HIV activities, both in free virus cellular infection and in a model of cell-cell viral transmission (virological synapse), which is the most effective mode of transmission and is often resistant to neutralizing antibodies and conventional antiviral drugs.

CD4-mimetic sulfopeptide conjugates display sub-nanomolar anti-HIV-1 activity and protect macaques against a SHIV162P3 vaginal challenge. Ariën KK, Baleux F, Desjardins D, Porrot F, Coïc YM, Michiels J, Bouchemal K, Bonnaffé D, Bruel T, Schwartz O, Le Grand R, Vanham G, Dereuddre-Bosquet N, Lortat-Jacob H.Scientific Reports;6:34829

Cryo-electron Microscopy Structure of the Native Prototype Foamy Virus Glycoprotein and Virus Architecture

Foamy viruses (FV) belong to the genus Spumavirus, which forms a distinct lineage in the Retroviridae family. Although the infection in natural hosts and zoonotic transmission to humans is asymptomatic, FVs can replicate well in human cells making it an attractive gene therapy vector candidate. Here the scientists of MEM and EBEV group present cryo-electron microscopy and (cryo-)electron tomography ultrastructural data on purified prototype FV (PFV) and PFV infected cells. Mature PFV particles have a distinct morphology with a capsid of constant dimension as well as a less ordered shell of density between the capsid and the membrane likely formed by the Gag N-terminal domain and the cytoplasmic part of the Env leader peptide gp18LP. The viral membrane contains trimeric Env glycoproteins partly arranged in interlocked hexagonal assemblies. In situ 3D reconstruction by subtomogram averaging of wild type Env and of a Env gp48TM- gp80SU cleavage site mutant showed a similar spike architecture as well as stabilization of the hexagonal lattice by clear connections between lower densities of neighboring trimers. Cryo-EM was employed to obtain a 9 Å resolution map of the glycoprotein in its pre-fusion state, which revealed extensive trimer interactions by the receptor binding subunit gp80SU at the top of the spike and three central helices derived from the fusion protein subunit gp48TM. Our ultrastructural data and 9 Å resolution glycoprotein structure provide important new insights into the molecular architecture of PFV and its distinct evolutionary relationship with other members of the Retroviridae.

Cryo-electron Microscopy Structure of the Native Prototype Foamy Virus Glycoprotein and Virus Architecture. Effantin G, Estrozi LF, Aschman N, Renesto P, Stanke N, Lindemann D, Schoehn G, Weissenhorn W. PLoS Pathogens;12(7):e1005721

X-rays Reveal New Path In Battle Against Mosquito-borne Illness

Could we get rid of mosquitoes without polluting the environment? Yes, we can! The BinAB toxin, produced in crystal form by a bacterium, specifically kills the larvae of Culex and Anopheles mosquitoes, but it is inactive on tiger mosquitoes (or Aedes), the vectors for dengue fever and chikungunya. Knowledge of the molecular structure of BinAB is necessary if we are to broaden its spectrum of action. Having long been inaccessible, this structure is now being published on 28 September 2016 in Nature by an international consortium involving scientists from the IBS, UCLA, UCR and SLAC in the USA.

Press release

De novo phasing with X-ray laser reveals mosquito larvicide BinAB structure . Jacques-Philippe Colletier, Michael R. Sawaya, Mari Gingery, Jose A. Rodriguez, Duilio Cascio, Aaron S. Brewster, Tara Michels-Clark, Robert H. Hice, Nicolas Coquelle, Sébastien Boutet, Garth J. Williams, Marc Messerschmidt, Daniel P. DePonte, Raymond G. Sierra, Hartawan Laksmono, Jason E. Koglin, Mark S. Hunter, Hyun-Woo Park, Monarin Uervirojnangkoorn, Dennis K. Bideshi, Axel T. Brunger, Brian A. Federici, Nicholas K. Sauter, David S. Eisenberg. Nature DOI: 10.1038/nature19825

Insights into the reaction mechanism of NadA enzyme

The enzyme NadA catalyzes the synthesis of quinolinic acid (QA), the precursor of the universal nicotinamide adenine dinucleotide (NAD), cofactor in many metabolic pathways. Despite the interest in this reaction, its mechanism is still controversial. We have solved the crystal structure of NadA in complexes with (i) the condensation product of its two substrates, (ii) an inhibitor of the reaction and (iii) QA, obtained by reacting substrates in the crystal. These complexes allowed us to shed light on the mechanism and the nature of the reaction intermediates. Given that NadA is a specific enzyme for several pathogens, this work will be crucial for the design of new antibiotic agents.

Crystal Structures of Quinolinate Synthase in Complex with a Substrate Analogue, the Condensation Intermediate, and Substrate-Derived Product. Anne Volbeda, Claudine Darnault, Oriane Renoux, Debora Reichmann, Patricia Amara, Sandrine Ollagnier de Choudens, and Juan C. Fontecilla-Camps. J. Am. Chem. Soc.;138(36):11802-9

Scientists use neutrons to understand the secrets of extremophile bacteria like the ones decomposing the RMS Titanic

Understanding microbe adaptation to extreme environments remains a challenge of high biotechnological potential—in bioremediation and waste management, for example. Halomonas microorganisms isolated from the oceans or salt marshes, reversibly accumulate high concentrations of the molecule ectoine, within their cells, to counterbalance fluctuating external salt concentrations. It has been estimated that a rust- producing Halomonas species could bring about the total deterioration of the sunken RMS Titanic by 2030. A range of specialised neutron scattering experiments were designed in order to understand how ectoine permits Halomonas to survive in their extreme environment. They revealed that within the microbe cells, ectoine acts by enhancing the remarkable dynamic properties of water that are essential to life processes.

Communiqué/Press release

Neutrons describe ectoine effects on water H-bonding and hydration around a soluble protein and a cell membrane. Giuseppe Zaccai, Irina Bagyan, Jérôme Combet, Gabriel J. Cuello, Bruno Demé, Yann Fichou, François-Xavier Gallat, Victor M. Galvan Josa, Susanne von Gronau, Michael Haertlein, Anne Martel, Martine Moulin, Markus Neumann, Martin Weik, and Dieter Oesterhelt. Scientific Reports. 6:31434

Decrypting a cellular guidance system to fight against pneumococcal infections

Accurate placement of the bacterial division site is a prerequisite for the generation of two viable and identical daughter cells. In Streptococcus pneumoniae (pneumococcus), the positive regulatory mechanism involving the membrane protein MapZ positions precisely the conserved cell division protein FtsZ at the cell centre. Reasearchers of the Institut de Biologie et de Chimie des Protéines in Lyon et of the NMR group of the IBS characterized the structure of the extracellular domain of MapZ. This structure–function analysis of MapZ, published in Nature Communications, provides the first molecular characterization of a positive regulatory process of bacterial cell division which may be helpfull to develop new antibiotics.

Structure–function analysis of the extracellular domain of the pneumococcal cell division site positioning protein MapZ. Sylvie Manuse, Nicolas L. Jean, Mégane Guinot, Jean-Pierre Lavergne, Cédric Laguri, Catherine M. Bougault, Michael S. VanNieuwenhze, Christophe Grangeasse & Jean-Pierre Simorre. Nature Communications, doi:10.1038/ncomms12071, Published 27 June 2016

Assembly kinetics of Transthyretin monitored by native mass spectrometry

TThe homotetrameric protein Transthyretin (TTR), responsible for the transport of thyroxine and retinol, is involved in amyloidosis, a disease characterized by the presence of deposits of insoluble molecular aggregates in tissue. The aggregation of the wild type (WT) TTR protein triggers a senile systemic amyloidosis mainly affecting the heart and causing polyneuropathy and / or familial amyloid cardiomyopathy. Over the years, many techniques have been used to study this protein and its folding and currently there are over 200 structures of TTR. Unfortunately, none of these data explained in detail the mechanism of the formation of amyloid fibrils.
Scientists of the IBS, the ILL, the ESRF and the Wolfson Institute for Biomedical Research (London, UK) have used MS, thioflavin T fluorescence, and crystallographic data (by NMR and neutron diffraction) to demonstrate that while the X-ray structures of unlabeled and deuterium-labeled TTR are essentially identical, subunit exchange kinetics and amyloid formation are accelerated for the deuterated protein. However, a slower subunit exchange is noted in deuterated solvent, reflecting the poorer solubility of nonpolar protein side chains in such an environment. These observations are important for the interpretation of kinetic studies involving deuteration and also to discover the mechanism of amyloidosis. Undoubtedly, details of the solvent structure and amino acid protonation states are crucial for better understanding amyloidosis. Neutron crystallographic studies of pathologically related TTR mutations are currently in progress.

Impact of Deuteration on Assembly Kinetics of Transthyretin Monitored by Native Mass Spectrometry and Implications for Amyloidosis. Ai Woon Yee, Martine Moulin, Nina Breteau, Michael Haertlein, Edward P. Mitchell, Jonathan B. Cooper, Elisabetta Boeri Erba*, V. Trevor Forsyth* (*Corresponding authors). Angew Chem Int Ed Engl. 2016 Jun 17. doi: 10.1002/anie.201602747

The start-up NMR-Bio is launched…

Founded on January 8, 2016, NMR-Bioled by Rime Kerfah, is a spin-off of IBS.

NMR-Bio specializes in technologies related to the bimolecular nuclear magnetic resonance NMR offering a broad range of customized research services and products.

NMR-Bio has a dynamic and dedicated team, consisting of two scientific advisers, Olivier Hamelin (UGA / BIG) and Jerome Boisbouvier (CNRS / IBS), and a R&D Isotope Labeling engineer researcher, Elodie Crublet, who joined NMR-Bio in March.

Kinetics and RNA sequence dependence of measles virus nucleocapsid

Measles virus RNA genomes are packaged into helical nucleocapsids (NCs), comprising thousands of nucleo-proteins (N) that bind the entire genome. N-RNA provides the template for replication and transcription by the viral polymerase and is a promising target for viral inhibition. The nucleocapsid assembly process regulating this process has been described for the first time by IBS researchers thanks to a combination of real-time NMR, fluorescence spectroscopy and electron microscopy. This observation is reported in Angewandte Chemie on June 06. Press release-(in french only)

Self-assembly of measles virus nucleocapsid-like particles: Kinetics and RNA sequence dependence. Sigrid Milles, Malene Ringkjøbing Jensen, Guillaume Communie, Damien Maurin, Guy Schoehn, Rob W.H. Ruigrok and Martin Blackledge. Angewandte Chemie, 30 May 2016

Integration of a hydrogenase on a TiO2 -coated p-Si photocathode for the photo-production of H2

The combination of hydrogenase from Desulfomicrobio bacutalum with semiconductors enables the photoelectrochemical
characterization of electron-transfer processes at highly active and well-defined catalytic sites on a light-harvesting electrode surface
Ce travail paru le 10 mai 2016 dans Angew Chem Int Ed Engl. est le fruit d’une collaboration avec le
This study was published in Angew Chem Int Ed Engl. on May 10, 2016 and was done in collaboration with Dr. Erwin Reisner (Department of Chemistry, University of Cambridge, Cambridge CB2 1EW (United Kingdom))

Photoelectrochemical H2 Evolution with a Hydrogenase Immobilized on a TiO2 -Protected Silicon Electrode. Lee CY, Park HS, Fontecilla-Camps JC, Reisner E. Angew Chem Int Ed Engl.;55(20):5971-4.

New insight into the dynamic behaviour of intrinsically disordered proteins

The dynamic nature of intrinsically disordered proteins (IDPs) defines their function, and yet we know very little about the nature of their dynamics. We measured extensive relaxation rates at multiple magnetic fields, at multiple temperatures and in different-length proteins to characterize in unprecedented detail the dynamic nature of an IDP from Sendai virus nucleoprotein. Using this detailed study we are able to develop a novel framework for understanding the behavior and function of IDPs.

Identification of Dynamic Modes in an Intrinsically Disordered Protein using Temperature-dependent NMR Relaxation. Abyzov A, Salvi N, Schneider R, Maurin D, Ruigrok RW, Jensen MR, Blackledge M. Journal of the American Chemical Society;138(19):6240-51

A progress in the search for an AIDS Vaccine

A sub-Saharan African donor’s blood has yielded remarkable finds that could be crucial in the search for an AIDS vaccine. An infected donor’s immune system naturally made potent antibodies, which lab tests showed could effectively recognize and neutralize about 50 percent of all HIV-1 strains circulating around the world. HIV-1 is the most widespread HIV type globally. Researchers managed to observe and understand the process of how the immune system developed these antibodies, which could advance vaccine design.
This study undertaken by scientists from the International AIDS Vaccine Initiative, The Scripps Research Institute, the University of California San Diego, Monogram Biosciences Inc., Rwanda-Zambia HIV Research Group, Academia Sinica, the Ragon Institute of MGH, MIT, and Harvard, and the Institut de Biologie Structurale was published on May 17 in the journal Immunity (Press release).

Early Antibody Lineage Diversification and Independent Limb Maturation Lead to Broad HIV-1 Neutralization Targeting the Env High-Mannose Patch. Daniel T. MacLeod, Nancy M. Choi, Bryan Briney, Fernando Garces, Lorena S. Ver, Elise Landais, Ben Murrell, Terri Wrin, William Kilembe, Chi-Hui Liang, Alejandra Ramos, Chaoran B. Bian, Lalinda Wickramasinghe, Leopold Kong, Kemal Eren, Chung-Yi Wu, Chi-Huey Wong, show The IAVI Protocol C Investigators & The IAVI African HIV Research Network, Sergei L. Kosakovsky Pond, Ian A. Wilson, Dennis R. Burton, Pascal Poignard. Immunity; DOI:

Binding to produce flowers

Press release

The LEAFY protein, a transcription factor responsible for flower development, is able to
assemble itself in small chains made up of several proteins. This mechanism allows it to
bind to and activate regions of the genome that are inaccessible to a single protein. These results were obtained by scientists in the Laboratoire de Physiologie Cellulaire Végétale and the Institut de Biologie Structurale, working in collaboration with their international partners. Published on 21 April 2016 in Nature Communications, they open the way to new research opportunities regarding the regulation of gene expression.

A SAM oligomerization domain shapes the genomic binding landscape of the LEAFY transcription factor. Sayou C, Nanao MH, Jamin M, Posé D, Thévenon E, Grégoire L, Tichtinsky G, Denay G, Ott F, Peirats Llobet M, Schmid M, Dumas R, Parcy F. Nature Communication;7:11222.

Filming a radical-based reaction at work

The Metalloproteins group at IBS, in collaboration with scientists from the IBS NMR group, INRA-AgroParisTech-Upsay and INAC describes for the first time the mechanism of a carbon–sulfur bond formation. They got a series of the snapshots of a radical-based reaction, hard to study in a protein. The carbon-sulfur bond is very difficult to form, yet this type of bond plays a key role in many medically relevant drugs. The results of this study are published in Nature Chemistry April 4, 2016.

​Carbon–sulfur bond-forming reaction catalysed by the radical SAM enzyme HydE. Roman Rohac, Patricia Amara, Alhosna Benjdia, Lydie Martin, Pauline Ruffié, Adrien Favier, Olivier Berteau, Jean-Marie Mouesca, Juan C. Fontecilla-Camps and Yvain Nicolet. Nature Chemistry DOI : 10.1038/nchem.2490

Serial femtosecond crystallography of the photoswitchable fluorescent protein IrisFP

Serial femtosecond crystallography (SFX) at an X-ray free electron laser (XFEL) exploits intense X-ray pulses to provide a diffraction pattern before radiation damage destroys the protein crystal. The sample is replenished millions of times and diffraction data collected in a serial way. SFX permits tiny microcrystals to be studied and enables time-resolved studies of proteins in action down to the femtosecond time scale.
As a proof-of-principle en route to time-resolved crystallographic experiments on fluorescent proteins, the static three-dimensional structure of the photoswitchable fluorescent protein IrisFP in its on state was solved by SFX. The high-quality structure shows no signs of X-ray radiation damage and was determined from a very small amount of crystalline sample. For this project, the IBS DYNAMOP group used the XFEL at SACLA in Japan and teamed up with scientists from SACLA, the Max-Planck Institute in Heidelberg, the Universities of Lille and Rennes and the ESRF in Grenoble.
As a complement to SFX, time-resolved absorption spectroscopy was used to identify picosecond to millisecond intermediate-states of IrisFP during photoswitching, which are assigned to a sequential process of isomerisation and proton transfer. Together, our data lay a solid ground for ultra-fast time-resolved SFX at XFELs of photoswitchable fluorescent proteins that, beyond their fascinating photochemistry, are of major importance for advanced nanoscopy, such as super-resolution microscopy.

Serial Femtosecond Crystallography and Ultrafast Absorption Spectroscopy of the Photoswitchable Fluorescent Protein IrisFP. Colletier JP, Sliwa M, Gallat FX, Sugahara M, Guillon V, Schiro G, Coquelle N, Woodhouse J, Roux L, Gotthard G, Royant A, Uriarte LM, Ruckebusch C, Joti Y, Byrdin M, Mizohata E, Nango E, Tanaka T, Tono K, Yabashi M, Adam V, Cammarata M, Schlichting I, Bourgeois D, Weik M (2016) The Journal of Physical Chemistry Letters: 882-887

A protein caught in act of evolution

​NosL is a radical S-adenosyl-L-methionine enzyme responsible for the radical-based conversion of L-tryptophan into 3-methylindolic acid, a key building block of the antibiotic nosiheptide. While exclusively used as feed additive for animal growth, nosiheptide has recently aroused new interest because of its high efficiency against multiresistant strains of several gram positive pathogens such as staphylococcus aureus. In the present study, using electron paramagnetic resonance spectroscopy, the Metalloproteins Unit at IBS and the LRM at INAC succesfully trapped and characterized a transient radical intermediate in the time course of the reaction catalyzed by NosL. This species shows that the enzyme performs an unexpected carboxyl radical migration instead of the Cα-Cβ bond break catalyzed by its relative tyrosine lyases.
NosL is a remarkable example of the evolution process for an enzyme to adapt and catalyze a new reaction, despite strong inherited structural constraints. In particular, NosL regained flexibility at its substrate binding site to fine-tune the radical-based chemistry and more particularly to select the C-C bond to cleave. However, the ancestral activity remains and compete with the physiological one. This unexpected flexibility suggests that radical SAM enzymes may be engineered to be used in synthetic biology. These results have been published in Science on March the 18th (Sicoli et al., Science 2016).

Fine-Tuning of a Radical-Based Reaction by Radical S-Adenosyl-L- Methionine Tryptophan Lyase
Giuseppe Sicoli, Jean-Marie Mouesca, Laura Zeppieri, Patricia Amara, Lydie Martin, Anne–Laure Barra, Juan C. Fontecilla-Camps, Serge Gambarelli, Yvain Nicolet

Bernard Jacrot, developer of Structural Biology in Grenoble, passes away

CEA engineer in the sixties, first French director of the ILL from 1967 to 1973, director of the EMBL’s Grenoble outstation from 1980 to 1990, Bernard Jacrot played a key role in the establishment of Structural Biology in Grenoble.

Bernard Jacrot graduated from France’s École Polytechnique with an Ingénieur degree in biophysics and a doctorate in physics joined the CEA as an engineer and became head of the CEA’s solid-state physics department. As early as 1962 he became an enthusiastic supporter of the project to create a Franco-German neutron research centre, which was finally to emerge as the ILL. It was only natural that he should become the ILL’s first French director in 1967, in a tandem arrangement with Prof. Heinz Maier-Leibnitz. As a neutron expert later specialising in biology, Bernard Jacrot was the ideal advocate for the use of neutrons in biological research.
Thereafter, he strongly encouraged Grenoble structuralists to join forces, initiating seminars and joint meetings and encouraging several physicists to discover the world of biology. Soon a laboratory of Structural Biology was established within the CENG and a CNRS Associated Research Unit (URA), gathered a largest group of researchers from diverse backgrounds (INSERM, CNRS, CEA, University, etc. ), who launched educational activities at the UJF and participation in the national Structural Biology DEA. Projects ImaBio (CNRS) and Protein 2000 (CEA) allowed the emergence of a French Structural Biology Center in Grenoble, IBS, a much-desired goal of the URA members to take full advantage of the proximity of two major instruments for structural biology : ESRF and ILL.
The work of the LSS and ILL Life Sciences groups, of the IBS and the PSB owes a huge amount to Bernard Jacrot and both IBS management and staff pay tribute in his memory and offer their condolences to his family and friends.

The dark side of photoconvertible fluorescent proteins

Photoconvertible fluorescent proteins are markers of choice for PhotoActivated Localization Microscopy (PALM). Notably, these markers allow counting target proteins one by one directly inside cells. Unfortunately, the accuracy of counting is limited by “blinking”, that is, the discontinuous character of light emission by a single fluorescent molecule along time. Indeed, a single molecule that blinks can easily be confounded with an ensemble of distinct molecules that appear successively at the same location. Blinking results from stochastic and reversible transitions between fluorescent and dark states, but the involved mechanisms remain poorly understood. Improving the quantitative analysis of PALM data thus relies on the design of low-blinking variants. By combining X-ray crystallography, optical spectroscopy and PALM microscopy, we discovered that the orientation of a unique, fully conserved, aminoacid located next to the chromophore entirely controls the blinking of photoconvertible fluorescent proteins. The knowledge of the orientation of this aminoacid (arginine 66) is then sufficient to accurately predict blinking properties. This research (that ANR refuses to finance …) brings new knowledge in fundamental photophysics and opens the door to the rational engineering of variants optimized for quantitative PALM.

Arginine 66 Controls Dark-State Formation in Green-to-Red Photoconvertible Fluorescent Proteins. Romain Berardozzi, Virgile Adam, Alexandre Martins et Dominique Bourgeois. Journal of the American Chemical Society;138(2):558-65.

ERC Consolidator Grant for Christophe Moreau

The European Research Council (ERC) has awarded a "Consolidator Grant" to Christophe Moreau for a project aiming at developing the Ion Channel-Coupled Receptor (ICCR) technology for in vitro diagnostic applications.

Christophe Moreau is a CNRS Researcher in the CHANNELS group of the Institut de Biologie Structurale (IBS - mixed research unit operated by CEA, CNRS and UGA). His project entitled ’NANOZ-ONIC’ will receive € 1.77 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 which are designed to support researchers at the stage at which they are consolidating their own independent research team or programme. The scheme strengthens independent and excellent new individual research teams that have been recently created.

What is this project about?
This ICCR technology will be interfaced with nano-electronic devices in partnership with Prof. Tai Hyun PARK and Prof. Seunghun HONG from the National University of Seoul. ICCRs were created in our group by linking membrane receptors, belonging to the G Protein Coupled Receptors (GPCRs) family, to an ion channel. When the receptor recognizes a specific molecule (ligand), the ion channel generates an electrical signal which is independent of intracellular signaling pathways and easily detectable by standard electrophysiological techniques or micro/nano-electronic devices.

CO and CN- syntheses by [FeFe]-hydrogenase maturase HydG

Hydrogenases, enzymes responsible for the production and consumption of molecular hydrogen, are characterized by having catalytic sites containing iron atoms linked to biologically atypical CO and CN- ligands. In the case of the FeFe enzymes these ligands are produced from tyrosine by HydG, a radical S-adenosyl-L-methionine-dependent enzyme. We have elucidated the catalytic mechanism of HydG and we show that, unexpectedly, the synthesis of CN and CO takes place at two well differentiated sites.

CO and CN- syntheses by [FeFe]-hydrogenase maturase HydG are catalytically differentiated events. Pagnier A, Martin L, Zeppieri L, Nicolet Y, Fontecilla-Camps JC. Proc Natl Acad Sci U S A. 2016 Jan 5;113(1):104-9.