A one-dimensional lattice model for a quantum mechanical free particle

Two types of particles, A and B with their corresponding antiparticles, are defined in a one dimensional cyclic lattice with an odd number of sites. In each step of time evolution, each particle acts as a source for the polarization field of the other type of particle with nonlocal action but with an effect decreasing with the distance: A -->...\bar{B} B \bar{B} B \bar{B} ... ; B --> A \bar{A} A \bar{A} A ... . It is shown that the combined distribution of these particles obeys the time evolution of a free particle as given by quantum mechanics.Comment: 8 pages. Revte

Structure of the Vesicular Stomatitis Virus N0-P Complex

Replication of non-segmented negative-strand RNA viruses requires the continuous supply of the nucleoprotein (N) in the form of a complex with the phosphoprotein (P). Here, we present the structural characterization of a soluble, heterodimeric complex between a variant of vesicular stomatitis virus N lacking its 21 N-terminal residues (NΔ21) and a peptide of 60 amino acids (P60) encompassing the molecular recognition element (MoRE) of P that binds RNA-free N (N0). The complex crystallized in a decameric circular form, which was solved at 3.0 Å resolution, reveals how the MoRE folds upon binding to N and competes with RNA binding and N polymerization. Small-angle X-ray scattering experiment and NMR spectroscopy on the soluble complex confirms the binding of the MoRE and indicates that its flanking regions remain flexible in the complex. The structure of this complex also suggests a mechanism for the initiation of viral RNA synthesis

Solution Structure of a Conformationally Restricted Fully Active Derivative of the Human Relaxin-like Factor

Analogous to insulin, the relaxin-like factor (RLF) must undergo a structural transition to the active form prior to receptor binding. Thus, the C terminus of the B chain of RLF folds toward the surface of the central B chain helix causing partial obliteration of the two essential RLF receptor-binding site residues valine-B19 and tryptophan-B27. Comparing the solution structure of a fully active C-terminally cross-linked RLF analog with native synthetic human RLF (hRLF) it became clear that the cross-linked analog largely retains the essential folding of the native protein. Both proteins exist in a major and minor conformation, as revealed by multiple resonances from tryptophan-B27 and adjacent residues on the B chain helix. Notably the minor conformation is significantly higher populated in the chemically cross-linked RLF than it is in hRLF. In addition, compared to the unmodified molecule subtle differences are observed within the B chain helix whereby the cross-linked derivative shows reduced hydrogen-bonding and significant peak broadening at the binding-site residue ValB19. Based on these observations we suggest that the solution structure of the native hormone represents an inactive conformer and that a dynamic equilibrium exists between the C-terminally unfolded binding conformation and the inactive conformation of RLF

Visualizing the molecular recognition trajectory of an intrinsically disordered protein using multinuclear relaxation dispersion NMR.

International audienceDespite playing important roles throughout biology, molecular recognition mechanisms in intrinsically disordered proteins remain poorly understood. We present a combination of (1)H(N), (13)C', and (15)N relaxation dispersion NMR, measured at multiple titration points, to map the interaction between the disordered domain of Sendai virus nucleoprotein (NT) and the C-terminal domain of the phosphoprotein (PX). Interaction with PX funnels the free-state equilibrium of NT by stabilizing one of the previously identified helical substates present in the prerecognition ensemble in a nonspecific and dynamic encounter complex on the surface of PX. This helix then locates into the binding site at a rate coincident with intrinsic breathing motions of the helical groove on the surface of PX. The binding kinetics of complex formation are thus regulated by the intrinsic free-state conformational dynamics of both proteins. This approach, providing high-resolution structural and kinetic information about a complex folding and binding interaction trajectory, can be applied to a number of experimental systems to provide a general framework for understanding conformational disorder in biomolecular function

Co-existing coupling schemes at high spin in

The nucleus 166Hf has been populated by the reaction 96Zr(74Ge,4n) using a beam energy of 310MeV. γ-rays were detected with the EUROBALL III detector array. Fourteen new normal-deformed rotational bands, of which six form coupled pairs, have been observed in 166Hf. Four previously known bands have been extended to considerably higher spin, and configurations of the new bands are proposed. Two different bands have been assigned configurations involving the same orbitals at high spin. The two coupling schemes, deformation and rotation alignment, are discussed in connection with this new observation, which calls for a formulation of co-existing coupling schemes in six-quasiparticle structures involving the same orbitals at high spin

On the use of pseudocontact shifts in the structure determination of metalloproteins

The utility of pseudocontact shifts in the structure refinement of metalloproteins has been evaluated using a native, paramagnetic Cu2+ metalloprotein, plastocyanin from Anabaena variabilis (A.v.), as a model protein. First, the possibility of detecting signals of nuclei spatially close to the paramagnetic metal ion is investigated using the WEFT pulse sequence in combination with the conventional TOCSY and 1H-15N HSQC sequences. Second, the importance of the electrical charge of the metal ion for the determination of correct pseudocontact shifts from the obtained chemical shifts is evaluated. Thus, using both the Cu+ plastocyanin and Cd2+-substituted plastocyanin as the diamagnetic references, it is found that the Cd2+-substituted protein with the same electrical charge of the metal ion as the paramagnetic Cu2+ plastocyanin provides the most appropriate diamagnetic reference signals. Third, it is found that reliable pseudocontact shifts cannot be obtained from the chemical shifts of the 15N nuclei in plastocyanin, most likely because these shifts are highly dependent on even minor differences in the structure of the paramagnetic and diamagnetic proteins. Finally, the quality of the obtained 1H pseudocontact shifts, as well as the possibility of improving the accuracy of the obtained structure, is demonstrated by incorporating the shifts as restraints in a refinement of the solution structure of A.v. plastocyanin. It is found that incorporation of the pseudocontact shifts enhances the precision of the structure in regions with only few NOE restraints and improves the accuracy of the overall structure. Copyright © 2006 John Wiley & Sons, Ltd

Structure of Nipah virus unassembled nucleoprotein in complex with its viral chaperone.

International audienceNipah virus (NiV) is a highly pathogenic emergent paramyxovirus causing deadly encephalitis in humans. Its replication requires a constant supply of unassembled nucleoprotein (N(0)) in complex with its viral chaperone, the phosphoprotein (P). To elucidate the chaperone function of P, we reconstituted NiV the N(0)-P core complex and determined its crystal structure. The binding of the N-terminal region of P blocks the polymerization of N by interfering with subdomain exchange between N protomers and keeps N(0) in an open conformation, ready to grasp an RNA molecule. We found that a peptide derived from the N-binding region of P protects cells against viral infection and demonstrated by structure-based mutagenesis that this peptide acts by inhibiting N(0)-P formation. These results provide new insights about the assembly of N along genomic RNA and validate the N(0)-P complex as a target for drug development

PED in 2021: A major update of the protein ensemble database for intrinsically disordered proteins

The Protein Ensemble Database (PED) (https://proteinensemble.org), which holds structural ensembles of intrinsically disordered proteins (IDPs), has been significantly updated and upgraded since its last release in 2016. The new version, PED 4.0, has been completely redesigned and reimplemented with cutting-edge technology and now holds about six times more data (162 versus 24 entries and 242 versus 60 structural ensembles) and a broader representation of state of the art ensemble generation methods than the previous version. The database has a completely renewed graphical interface with an interactive feature viewer for region-based annotations, and provides a series of descriptors of the qualitative and quantitative properties of the ensembles. High quality of the data is guaranteed by a new submission process, which combines both automatic and manual evaluation steps. A team of biocurators integrate structured metadata describing the ensemble generation methodology, experimental constraints and conditions. A new search engine allows the user to build advanced queries and search all entry fields including cross-references to IDP-related resources such as DisProt, MobiDB, BMRB and SASBDB. We expect that the renewed PED will be useful for researchers interested in the atomic-level understanding of IDP function, and promote the rational, structure-based design of IDP-targeting drugs.Fil: Lazar, Tamas. Vrije Unviversiteit Brussel; BélgicaFil: Martinez Perez, Elizabeth. European Molecular Biology Laboratory; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Quaglia, Federica. Università di Padova; ItaliaFil: Hatos, András. Università di Padova; ItaliaFil: Chemes, Lucia Beatriz. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Iserte, Javier Alonso. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Méndez, Nicolás Agustín. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Garrone, Nicolás Agustín. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Saldaño, Tadeo Enrique. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnologia. Laboratorio de Quimica y Biologia Computacional.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Marchetti, Julia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnologia. Laboratorio de Quimica y Biologia Computacional.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Velez Rueda, Ana Julia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnologia. Laboratorio de Quimica y Biologia Computacional.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bernadó, Pau. Centre National de la Recherche Scientifique; FranciaFil: Blackledge, Martin. Universite Grenoble Alpes; Francia. Centre National de la Recherche Scientifique; FranciaFil: Cordeiro, Tiago N.. Centre National de la Recherche Scientifique; Francia. Universidade Nova de Lisboa; PortugalFil: Fagerberg, Eric. Lund University; SueciaFil: Forman Kay, Julie D. University Of Toronto. Hospital For Sick Children; Canadá. University of Toronto; CanadáFil: Fornasari, Maria Silvina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnologia. Laboratorio de Quimica y Biologia Computacional.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gibson, Toby James. European Molecular Biology Laboratory; AlemaniaFil: Gomes, Gregory Neal W. University of Toronto; CanadáFil: Gradinaru, Claudiu C.. University of Toronto; CanadáFil: Head Gordon, Teresa. University of California; Estados UnidosFil: Jensen, Malene Ringkjøbing. Universite Grenoble Alpes; Francia. Centre National de la Recherche Scientifique; FranciaFil: Lemke, Edward A. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Longhi, Sonia. Centre National de la Recherche Scientifique; FranciaFil: Marino Buslje, Cristina. Fundación Instituto Leloir; ArgentinaFil: Minervini, Giovanni. Università di Padova; ItaliaFil: Mittag, Tanja. St. Jude Children's Research Hospital; Estados UnidosFil: Monzon, Alexander Miguel. Università di Padova; ItaliaFil: Pappu, Rohit V.. Washington University in St. Louis; Estados UnidosFil: Parisi, Gustavo Daniel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnologia. Laboratorio de Quimica y Biologia Computacional.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin