Institut de Biologie StructuraleGrenoble / France

2007

The enamine intermediate may not be universal to thiamine catalysis

Amara P, Fdez Galvan I, Fontecilla-Camps JC and Field MJ
Angewandte Chemie International Edition //England// (2007) *46*(47): 9019-9022

Books

Biophysical Analysis of Membrane Proteins: Investigating Structure and Function

Eva Pebay-Peyroula published a book entitled "Biophysical Analysis of Membrane Proteins : Investigating Structure and Function".
This book discusses new ways of using biophysical analysis to investigate the structure and function of membrane proteins. These proteins play an important role in many diseases and are fundamental to cellular function, but are still difficult to investigate.
Christine Ebel, Zaccai and Katy Jo Wood also collaborated on the production of this manual, published by John Wiley and Sons Ltd

Microtubule Protocols

Frank Kozielski, Salvator Debonis and Dimitrios Skoufias participated in the drafting of the 137th volume of the series "Methods in Molecular Medicine" entitled "Microtubule Protocols". They collaborated on the writing of chapter "Screening for Inhibitors of Microtubule-Associated Proteins Motor" (pp. 189-207).

This book contains a comprehensive collection of essential up-to-date methods used to study the biology of microtubules and the mechanisms of action of microtubule-interacting drugs.

Les Nanosciences. Tome 3. Nanobiotechnologies et Nanobiologie

Eric Forest collaborated on the writing of the book "Nanosciences. Volume 3. Nanobiotechnologies et Nanobiologie " (chapter "mass spectrometry").

ATAQS: a simulation method with applications to protein structure analysis and design )

Adaptive torsion-angle quasi-statics: a general simulation method with applications to protein structure analysis and design.
Rossi R, Isorce M, Morin S, Flocard J, Arumugam K, Crouzy S, Vivaudou M, Redon S.
Bioinformatics 23:i408-i419

Structure/Function Relationships of [NiFe]and [FeFe]Hydrogenases.

Fontecilla-Camps JC, Volbeda A, Cavazza C, Nicolet Y.
Chemical Review 2007 Oct;107(10):4273-303.

Structural insights into the Slit-Robo complex

Morlot C, Thielens NM, Ravelli RB, Hemrika W, Romijn RA, Gros P, Cusack S, McCarthy AA.
Proc. Natl. Acad. Sci. USA 104:14923-14928.

Coupling of protein and hydration water dynamics in biological membranes.

Coupling of protein and hydration water dynamics in biological membranes.
Wood, K., Plazanet, M., Kessler, B., Gabel, F., Oesterhelt, D., Tobias, D., Zaccai, G. & Weik, M.
Proc. Natl. Acad. Sci. Oct.29

The IBS organised Open Days from October 10 to 14, 2007

The 16th edition of the Science Week took place from the 5th to the 14th of October, 2007. For this edition the Institute welcomed the general public (adults and secondary school pupils) and invited them to discover the world of living on the atomic scale.

For this occasion a reportage was made by FRANCE 3 television :reportage at the IBS (13Mo)

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Crédit photo : IBS/CEA-CNRS-UJF

Structural and mechanistic basis of penicillin-binding protein inhibition by lactivicins.

Macheboeuf, P., Fischer, D. S., Brown Jr., T., Zervosen, A., Luxen, A., Joris, B., Dessen, A. & Schofield, C. J.
Nature Chem. Biol., 2007, Aug 5

Mapping the conformational landscape of urea-denatured ubiquitin using residual dipolar couplings.

Meier S, Grzesiek S, Blackledge M.

J Am Chem Soc. 129:9799-9807.

New light on regulation mechanisms of bacterial resistance against beta-lactam antibiotics

Conformational and thermodynamic changes of the repressor/DNA operator complex upon monomerization shed new light on regulation mechanisms of bacterial resistance against beta-lactam antibiotics.

Boudet J, Duval V, Van Melckebeke H, Blackledge M, Amoroso A, Joris B, Simorre JP.

Nucleic Acids Res. 35:4384-4395.

Sequence and expression differences underlie functional specialization of Arabidopsis microRNAs miR159 and miR319.

Palatnik JF, Wollmann H, Schommer C, Schwab R, Boisbouvier J, Rodriguez R, Warthmann N, Allen E, Dezulian T, Huson D, Carrington JC and Weigel D

Developmental Cell (2007) 13(1): 115-125

Protein folding and unfolding studied at atomic resolution by fast two-dimensional NMR spectroscopy.

Schanda P, Forge V, Brutscher B
Proc Natl Acad Sci U S A. 2007 Jul 3;104(27):11257-62.
For details, please read the french version.

IBS flyer

Dedicated to the general public as well as our scientific community, industrial research teams or students, this document presents the IBS.

IBS flyer (pdf file) (420 Ko)

How to prevent pathogenic bacteria from synthetising needles that are required for secretion of toxins into host cells.

Structure of the heterotrimeric complex that regulates type III secretion needle formation.
Quinaud M, Ple S, Job V, Contreras-Martel C, Simorre JP, Attree I and Dessen A
Proceedings of the National Academy of Sciences U S A (2007) 104(19): 7803-780

3D structure of a protein involved in Alzheimer’s disease

Highly Populated Turn Conformations in Natively Unfolded Tau Protein Identified from Residual Dipolar Couplings and Molecular Simulation.
Mukrasch M,Markwick P, Biernat J, Bergen MV, Bernado P, Griesinger C, Mandelkow E, Zweckstetter M and Blackledge M.
J Am Chem Soc. 129 (16), 5235 -5243

Automated spectral compression for fast multidimensional NMR and increased time resolution in real-time NMR spectroscopy.

Lescop E, Schanda P, Rasia R and Brutscher B

Journal of the American Chemical Society (2007);129;(10): 2756-2757

Amino acid bulkiness defines the local conformations and dynamics of natively unfolded alpha-synuclein and tau

Cho MK, Kim HY, Bernado P, Fernandez CO, Blackledge M and Zweckstetter M

Journal of the American Chemical Society (2007) 129(11): 3032-3033

Modular structure of the full-length DNA gyrase B subunit revealed by small-angle X-ray scattering

Costenaro L, Grossmann GJ, Ebel C, Maxwell A.

Structure 15, 329.

The binding site of the innate immune recognition protein MBL for its associated proteases

Identification of the site of human mannan-binding lectin involved in the interaction with its partner serine proteases: the essential role of Lys55.

Teillet F, Lacroix M, Thiel S, Weilguny D, Agger T, Arlaud GJ, Thielens NM.

J. Immunol. 178, 5710-5716.

Filming a protein at work by kinetic crystallography ! (Science)

Most of the research done on proteins is based on their study in a resting state. Their study in movement is extremely challenging due to technological limitations. The “kinetic crystallography” team of the IBS, in collaboration with the ESRF and the iRTSV (CEA), has made a movie of an enzyme executing its biological function. The enzyme is called superoxide reductase and is involved in the important issue of “oxydative stress”. The achievement of this research is two-fold: first, a new methodology combining crystallography and Raman spectroscopy is proposed to record structural snapshots of proteins in action; second, the results on superoxide reductase contribute to the precise understanding of how this enzyme works.

Raman-assisted crystallography reveals end-on peroxide intermediates in a nonheme iron enzyme.

Katona G, Carpentier P, Niviere V, Amara P, Adam V, Ohana J, Tsanov N, Bourgeois D.

Science 2007 Apr 20;316(5823):449-53

Details :

Superoxide reductase eliminates a dangerous molecule called the “superoxide radical”, which is produced by outflows of the oxygen metabolism. In humans, about 2% of the oxygen used to breathe is transformed into this toxic superoxide radical molecule, instead of water. This production is increased in people affected by neurogenerative diseases such as Alzheimer. The high amount of these molecules in turn contribute to worsen these illnesses, so scientists are looking for drugs to eliminate them.

Superoxide reductase acts uniquely in bacteria and its counterpart for humans (superoxide dismutase) carries out a more complex reaction. Understanding the chemical tricks used by superoxide reductase not only is of fundamental importance in the field of iron biochemistry, but could also open exciting possibilities for developing future drugs.

A struck of luck allowed to produce the film: in a single crystal, three intermediate states could be trapped at once by freezing the sample at an appropriate moment after the reaction was triggered. This resulted from the fact that, in the crystal, several nominally identical active sites experience slightly different packing forces, creating slight differences between them. In order to make sure that the right intermediate states were trapped, the technique of in crystallo Raman spectroscopy was developped at the “Cryobench” laboratory (ESRF-IBS). This technique provided strong evidence that the states were biologically relevant. Synchrotron x-rays were then used to decipher their three dimentional structures. It is expected that this new methodology will be of use for many researchers in the field.

Several hypothesis for the mechanism of superoxide reductase have been inferred in the past. The binding mode of the superoxide radical, the role of some key amino-acid residues, and the direct participation of a water molecule in catalysis were anticipated. Our direct visualization of these events allow a better understanding of how all these elements fit together to actually do the job of transforming the superoxide radical into the reaction product, hydrogen peroxide. We found that a key lysine residue moves around at the surface of the enzyme to grab a water molecule from the surrounding and brings it into the enzyme active site, at a very strategic point where this water molecule may donate a proton to the substrate (Figure). Many puzzling questions remain, however, which will be adressed in future experiments.

IBS scientific Day

This year the “IBS scientific day“ was held on Friday 20 April 2007.

It was the occasion for some IBS scientists, PhD and masters students to give an overview of their research to the whole IBS staff.

IBS Newsletter

You can now consult the latest scientific news from our laboratories, in IBS Actualités, the IBS scientific newsletter.

Structure and nuclear import function of the C-terminal domain of influenza virus polymerase PB2 subunit (Nat Struct Mol Biol.)

Tarendeau F, Boudet J, Guilligay D, Mas PJ, Bougault CM, Boulo S, Baudin F, Ruigrok RW, Daigle N, Ellenberg J, Cusack S, Simorre JP, Hart DJ.
Nat Struct Mol Biol. 2007 Mar;14(3):229-33.

Direct Observation of Dipolar Couplings and Hydrogen Bonds across a beta-Hairpin in 8 M Urea

Meier, S.; Strohmeier, M.; Blackledge, M.; Grzesiek, S.

J. Am. Chem. Soc.; 129; 754-755 (2007).

UltraSOFAST HMQC NMR and the Repetitive Acquisition of 2D Protein Spectra at Hz Rates

Gal, M.; Schanda, P.; Brutscher, B.; Frydman, L.

J. Am. Chem. Soc.; 129; 1372-1377 (2007).

A new type of water behaviour within the cells of a Dead sea organism PNAS)

“Salt-loving” cells, named halophiles, are a class of extremophiles, their study can teach us a great deal about the ability of living organisms to adapt to extreme conditions on earth. It may even help us in our search for signs of life on another planet. The discovery related here will help us to understand the interactions that occur between biological systems and water.

Liquid water is a highly dynamic flickering structure of bonds. Water in living cells is slightly slowed down compared to liquid water. The water discovered in the cells of ancient organisms that live in the saturated salt waters of the Dead Sea is one thousand times slower indicating especially strong interactions that may be similar to those occurring for certain proteins in human cells.

The report on this close collaboration between the IBS, the ILL, and German and Israeli laboratories, has been published on 10 January 2007 in the Proceedings of the National Academy of Sciences of the United States of America (PNAS). The paper makes the cover of this prestigious scientific journal, and is reported in NATURE vol.445 as a Research Highlight.

Neutron scattering reveals extremely slow cell water in a Dead Sea organism

PNAS, 2007 Jan 16;104(3):766-71.

Tehei M, Franzetti B, Wood K, Gabel F, Fabiani E, Jasnin M, Zamponi M, Oesterhelt D, Zaccai G, Ginzburg M, Ginzburg BZ.

Structural insights into the innate immune recognition specificities of L- and H-ficolins

Garlatti, V., Belloy, N., Martin, L., Lacroix, M., Matsushita, M., Endo, Y., Fujita, T., Fontecilla-Camps, J.C., Arlaud, G.J., Thielens, N.M. & Gaboriaud, C. (2007)

EMBO J. 26, 623-633.

Recognition proteins of innate immunity : more varied functions than anticipated

Vue détaillée de l’interaction de l’acide sialique (Neu5Ac, en jaune) dans le site S1 de la ficoline M.

Structural basis for innate immune sensing by M-ficolin and its control by a pH-dependent conformational switch. V. Garlatti, L. Martin, E. Gout, J.-B. Reiser, T. Fujita, G.J. Arlaud, N.M. Thielens, C. Gaboriaud (2007). J. Biol. Chem. 282, 35814-35820.

Structural insights into the innate immune recognition specificities of L- and H-ficolins. V. Garlatti, N. Belloy, L. Martin, M. Lacroix, M. Matsushita, Y. Endo, T. Fujita, J.C. Fontecilla-Camps, G.J. Arlaud, N.M. Thielens, C. Gaboriaud (2007) EMBO J., 26, 623-633.

Crystal structure of Arabidopsis thaliana indole-3-acetic acid methyltransferase, a key regulation point of auxin homeostasis in plant.

The crystal structure of Arabidopsis thaliana indole-3-acetic acid methyltransferase (IAMT) was determined and refined to 2.75 Å resolution. IAMT is a member of the SABATH family that modulates IAA homeostasis in plant tissues through the methylation of IAA’s free carboxyl group.

Structural, Biochemical and Phylogenetic Analyses Suggest that Indole-3-acetic Acid ethyltransferase Is An Evolutionarily Ancient Member of the SABATH Family
Nan Zhao, Jean-Luc Ferrer, Jeannine Ross, Ju Guan, Yue Yang, Eran Pichersky, Joseph P. Noel, and Feng Chen,
Plant Physiol., 2007 Dec 27

Hyperdimensional protein NMR Spectroscopy in peptide sequence space

Lescop E, Brutscher B
J.Am.Chem. Soc. 129 :11916-11917.