Calligari P.A.,Ecole Normale Superieure de Paris |
Kneller G.R.,CNRS Center for Molecular Biophysics |
Kneller G.R.,Synchrotron Soleil
Acta Crystallographica Section D: Biological Crystallography | Year: 2012
A new application of the ScrewFit algorithm [Kneller & Calligari (2006), Acta Cryst. D62, 302-311] is presented which adds the detection of protein secondary-structure elements to their detailed geometrical description in terms of a curve with intrinsic torsion. The extension is based on confidence and persistence criteria for the ScrewFit parameters which are established by analyzing the structural fluctuations of standard motifs in the SCOP fold classes. The agreement with the widely used DSSP method is comparable with the general consensus among other methods in the literature. This combination of secondary-structure detection and analysis is illustrated for the enzyme adenylate kinase.© 2012 International Union of Crystallography Printed in Singapore - all rights reserved.
Bunzli J.-C.G.,Korea University |
Bunzli J.-C.G.,Ecole Polytechnique Federale de Lausanne |
Eliseeva S.V.,CNRS Center for Molecular Biophysics |
Eliseeva S.V.,Institute for Advanced Studies
Chemical Science | Year: 2013
The enthralling properties of lanthanide luminescence have propelled luminescent probes, tags and materials based on these elements to the forefront of science and technology. In this minireview, attention is focused on the latest innovations and on less-known aspects of this field. Exciting new developments in bioimaging, therapy, drug delivery, security tags, luminescent sensors, and solar energy conversion are highlighted. © 2013 The Royal Society of Chemistry.
Piazza F.,CNRS Center for Molecular Biophysics
Physical Biology | Year: 2014
In this paper we propose a novel theoretical framework for interpreting long-range dynamical correlations unveiled in proteins through NMR measurements. The theoretical rationale relies on the hypothesis that correlated motions in proteins may be reconstructed as large-scale, collective modes sustained by long-lived nonlinear vibrations known as discrete breathers (DB) localized at key, hot-spot sites. DBs are spatially localized modes, whose nonlinear nature hinders resonant coupling with the normal modes, thus conferring them long lifetimes as compared to normal modes. DBs have been predicted to exist in proteins, localized at few hot-spot residues typically within the stiffest portions of the structure. We compute DB modes analytically in the framework of the nonlinear network model, showing that the displacement patterns of many DBs localized at key sites match to a remarkable extent the experimentally uncovered correlation blueprint. The computed dispersion relations prove that it is physically possible for some of these DBs to be excited out of thermal fluctuations at room temperature. Based on our calculations, we speculate that transient energy redistribution among the vibrational modes in a protein might favor the emergence of DB-like bursts of long-lived energy at hot-spot sites with lifetimes in the ns range, able to sustain critical, function-encoding correlated motions. More generally, our calculations provide a novel quantitative tool to predict fold-spanning dynamical pathways of correlated residues that may be central to allosteric cross-talk in proteins. © 2014 IOP Publishing Ltd.
Divita G.,CNRS Center for Molecular Biophysics
Chemistry and Biology | Year: 2010
Jones et al. (2010) propose an innovative strategy for the development of bioactive cell-penetrating peptides. They combine computer-based design with specific targeting to elaborate a potent cell-penetrating bioactive peptide derived from cytochrome C. This short chimera peptide induces tumor cell apoptosis by targeting and sequestering nucleoporin, a key component of the nuclear pore complex. © 2010 Elsevier Ltd.
Fiorini F.,French Institute of Health and Medical Research |
Boudvillain M.,CNRS Center for Molecular Biophysics |
Hir H.L.,French Institute of Health and Medical Research
Nucleic Acids Research | Year: 2013
The RNA helicase Upf1 is a multifaceted eukaryotic enzyme involved in DNA replication, telomere metabolism and several mRNA degradation pathways. Upf1 plays a central role in nonsense-mediated mRNA decay (NMD), a surveillance process in which it links premature translation termination to mRNA degradation with its conserved partners Upf2 and Upf3. In human, both the ATP-dependent RNA helicase activity and the phosphorylation of Upf1 are essential for NMD. Upf1 activation occurs when Upf2 binds its N-terminal domain, switching the enzyme to the active form. Here, we uncovered that the C-terminal domain of Upf1, conserved in higher eukaryotes and containing several essential phosphorylation sites, also inhibits the flanking helicase domain. With different biochemical approaches we show that this domain, named SQ, directly interacts with the helicase domain to impede ATP hydrolysis and RNA unwinding. The phosphorylation sites in the distal half of the SQ domain are not directly involved in this inhibition. Therefore, in the absence of multiple binding partners, Upf1 is securely maintained in an inactive state by two intramolecular inhibition mechanisms. This study underlines the tight and intricate regulation pathways required to activate multifunctional RNA helicases like Upf1. © The Author(s) 2012. Published by Oxford University Press.