Structural Insights into the Role of Diphthamide on Elongation Factor 2 in mRNA Reading-Frame Maintenance

© 2018 Elsevier Ltd One of the most critical steps of protein biosynthesis is the coupled movement of mRNA, which encodes genetic information, with tRNAs on the ribosome. In eukaryotes, this process is catalyzed by a conserved G-protein, the elongation factor 2 (eEF2), which carries a unique post-translational modification, called diphthamide, found in all eukaryotic species. Here we present near-atomic resolution cryo-electron microscopy structures of yeast 80S ribosome complexes containing mRNA, tRNA and eEF2 trapped in different GTP-hydrolysis states which provide further structural insights into the role of diphthamide in the mechanism of translation fidelity in eukaryotes

МОДЕЛИРОВАНИЕ ГИДРОГЕОМЕХАНИЧЕСКИХ ПЛАСТОВЫХ ПРОЦЕССОВ ПУТЕМ ВНЕШНЕГО СОПРЯЖЕНИЯ СПЕЦИАЛИЗИРОВАННЫХ ВЫЧИСЛИТЕЛЬНЫХ ПАКЕТОВ И УНИВЕРСАЛЬНОЙ CAE FIDESYS

We study several algorithms for solving the coupled problem of hydrogeomechanical modeling of fluid filtration in a deformed  fractured rock, allowing to describe the mutual influence of filtration  and rock deformation processes on the dynamic parameters of the  medium: porosity, permeability, rock stiffness and fracture  extensions. These algorithms allow solving the problems of choosing  the location and drilling trajectory of a well either wellbore stability,  ensuring high productivity of the formation due to optimization of  the design of hydraulic fracturing and sand control. Together with seismic and reservoir testing data, coupled hydrogeomechanical  modeling allows optimizing the tactics and strategy of reservoir  development. The disturbance of formation stress-strain state in the  near-well zone leads to the development of deformation processes and fracture zones, as well as changes in pore pressure and filtration properties in the reservoir. At the first stage, we verify external and  internal iterative external coupling procedures. The specially  developed research code was used for internal coupling procedure.  For external coupling, a finite element simulator FIDESYS was used  which solves numerically the problems of geomechanical stresses  and deformation distributions in the rock. We developed the control  module to organize the iterative process of geomechanical and  hydrodynamic simulators, including reading special simulation data formats, unit conversion, as well as the value fields projection on  different model grids. In this paper, we present the modeling for  several problems and discuss the computation results. Effective  elastic-strength properties are determined numerically at every  mesh node as a result of solving the time consuming spatial  elastoplastic problem. Therefore, the reduction in the frequency of  data exchange is important in this approach. One of the goals of this numerical study, related to the above methodology, is to determine the effect of the coupling frequency on the solution. Based on the  computation results for the example of the cyclic CO2 injection  procedure in the Bazhenov Formation formation (Palyanovo section), only the local production characteristics are sensitive to  the coupling frequency. The results obtained in this paper allow us to conclude that the role of geomechanical effects of fractured rock deformations saturated with a fluid is significant for modeling the formation  processes.В статье рассматриваются различные алгоритмы решения связанной задачи  гидрогеомеханического моделирования фильтрации жидкости в деформируемой  трещиноватой породе, позволяющие учитывать взаимное влияние процессов фильтрации и  деформирования горных пород на динамические параметры среды: пористость,  проницаемость, жесткость породы и раскрытие трещин. Данные алгоритмы позволяют  решать задачи о выборе места и траектории бурения скважины и их устойчивости, об  обеспечении высокой продуктивности пласта за счет оптимизации дизайна ГРП и контроля  за пескопроявлением. Мониторинг естественного напряженно-деформированного состояния, в окрестности скважины при добыче углеводородов, позволяет предотвратить развитие  процессов деформации и образования зон разрушения. На первой стадии авторами  проводилась верификация процедуры итерационного внешнего сопряжения и процедуры  итерационного внутреннего сопряжения. При внутреннем сопряжении использовался специально разработанный авторами исследовательский код, в задачи которого входит организация итерационного процесса работы геомеханического и гидродинамического  симуляторов, чтение форматов данных симуляторов, преобразование единиц измерения  величин, а также проекция полей величин на различные модельные сетки. Для внешнего  сопряжения был использован симулятор “CAE FIDESYS”, численно решающий задачи о  распределении геомеханических напряжений и деформаций в горной породе методами  конечных элементов. В данной работе приводятся результаты численного моделирования экспериментального варианта разработки месторождения, с приближенными к реальной среде свойствами. Одной из целей проводимых вычислений является определение влияния  степени сопряжения алгоритма, реализующего данную методику, на результат. В связи с  тем, что эффективные упруго-прочностные свойства численно определяются в каждой точке пространства в результате решения пространственной упругопластической задачи,  сокращение частоты обмена данными является важным в данном подходе. По результатам  расчетов на примере процедуры циклической закачки СО2 в формации Баженовской свиты (Пальяновский разрез) определено, что локальные характеристики добычи чувствительны к степени сопряжения. Полученные в статье результаты позволяют сделать вывод о важности учета геомеханических эффектов деформирования трещиноватых горных пород,  насыщенных жидкостью, при моделировании внутрипластовых процессов

Structure of the 70S ribosome from human pathogen Staphylococcus aureus

© 2016 The Author(s).Comparative structural studies of ribosomes from various organisms keep offering exciting insights on how species-specific or environment-related structural features of ribosomes may impact translation specificity and its regulation. Although the importance of such features may be less obvious within more closely related organisms, their existence could account for vital yet species-specific mechanisms of translation regulation that would involve stalling, cell survival and antibiotic resistance. Here, we present the first full 70S ribosome structure from Staphylococcus aureus, a Gram-positive pathogenic bacterium, solved by cryo-electron microscopy. Comparative analysis with other known bacterial ribosomes pinpoints several unique features specific to S. aureus around a conserved core, at both the protein and the RNA levels. Our work provides the structural basis for the many studies aiming at understanding translation regulation in S. aureus and for designing drugs against this often multi-resistant pathogen

Erratum: Structure of the 70S ribosome from human pathogen Staphylococcus aureus (Nucleic Acids Research (2017) DOI: 10.1093/nar/gkw933)

© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.The authors wish to correct their Funding statement as follows: FUNDING. 'Centre National de la Recherche Scientifique' (CNRS) and the 'Agence Nationale de la Recherche' as part of the 'Investissements d'Avenir' program [LabEx: ANR-10-LABX-0036-NETRNA to P.R., Y.H.; ANR-15-CE11-0021-01 to G.Y.]; 'Fondation pour la Recherche Médicale en France' [FDT20140930867 to I.K; 'European Research Council advanced grant' [294312 to M.Y.]; the 'Russian Science Foundation' [Project No. 16-14-10014 to I.K., M.Y.]. Funding for open access charge: Centre National de la Recherche Scientifique (CNRS). In addition, Marat Yusupov is associated with both affiliations1 and 2. The authors apologise to the readers for this error

Free Energy Simulations of a GTPase: GTP and GDP Binding to Archaeal Initiation Factor 2

International audienceArchaeal initiation factor 2 (aIF2) is a protein involved in the initiation of protein biosynthesis. In its GTP-bound, "ON" conformation, aIF2 binds an initiator tRNA and carries it to the ribosome. In its GDP-bound, "OFF" conformation, it dissociates from tRNA. To understand the specific binding of GTP and GDP and its dependence on the ON or OFF conformational state of aIF2, molecular dynamics free energy simulations (MDFE) are a tool of choice. However, the validity of the computed free energies depends on the simulation model, including the force field and the boundary conditions, and on the extent of conformational sampling in the simulations. aIF2 and other GTPases present specific difficulties; in particular, the nucleotide ligand coordinates a divalent Mg(2+) ion, which can polarize the electronic distribution of its environment. Thus, a force field with an explicit treatment of electronic polarizability could be necessary, rather than a simpler, fixed charge force field. Here, we begin by comparing a fixed charge force field to quantum chemical calculations and experiment for Mg(2+):phosphate binding in solution, with the force field giving large errors. Next, we consider GTP and GDP bound to aIF2 and we compare two fixed charge force fields to the recent, polarizable, AMOEBA force field, extended here in a simple, approximate manner to include GTP. We focus on a quantity that approximates the free energy to change GTP into GDP. Despite the errors seen for Mg(2+):phosphate binding in solution, we observe a substantial cancellation of errors when we compare the free energy change in the protein to that in solution, or when we compare the protein ON and OFF states. Finally, we have used the fixed charge force field to perform MDFE simulations and alchemically transform GTP into GDP in the protein and in solution. With a total of about 200 ns of molecular dynamics, we obtain good convergence and a reasonable statistical uncertainty, comparable to the force field uncertainty, and somewhat lower than the predicted GTP/GDP binding free energy differences. The sign and magnitudes of the differences can thus be interpreted at a semiquantitative level, and are found to be consistent with the experimental binding preferences of ON- and OFF-aIF2

The BM@N spectrometer at the NICA accelerator complex

BM@N (Baryonic Matter at Nuclotron) is the first experiment operating and taking data at the Nuclotron/NICA ion-accelerating complex.The aim of the BM@N experiment is to study interactions of relativistic heavy-ion beams with fixed targets. We present a technical description of the BM@N spectrometer including all its subsystems.Comment: 34 pages, 47 figures, 6 table

DNA-measuring Wadjet SMC ATPases restrict smaller circular plasmids by DNA cleavage.

Structural maintenance of chromosome (SMC) complexes fold DNA by loop extrusion to support chromosome segregation and genome maintenance. Wadjet systems (JetABCD/MksBEFG/EptABCD) are derivative SMC complexes with roles in bacterial immunity against selfish DNA. Here, we show that JetABCD restricts circular plasmids with an upper size limit of about 100 kb, whereas a linear plasmid evades restriction. Purified JetABCD complexes cleave circular DNA molecules, regardless of the DNA helical topology; cleavage is DNA sequence nonspecific and depends on the SMC ATPase. A cryo-EM structure reveals a distinct JetABC dimer-of-dimers geometry, with the two SMC dimers facing in opposite direction-rather than the same as observed with MukBEF. We hypothesize that JetABCD is a DNA-shape-specific endonuclease and propose the "total extrusion model" for DNA cleavage exclusively when extrusion of an entire plasmid has been completed by a JetABCD complex. Total extrusion cannot be achieved on the larger chromosome, explaining how self-DNA may evade processing

Nordic walking for police officers

The article reveals the sport – Nordic walking for physical training lessons by police officers. Nordic walking with sticks (Nordic walking, Nordic walking, Nordic walking) - a special kind of Amateur sport, representing a Hiking trip, during which walking is based on a special stick, which resembles a skiВ статье раскрывается вид спорта – скандинавская ходьба для занятий по физической подготовке с сотрудниками полиции. Скандинавская ходьба с палками (северная ходьба, нордическая ходьба, финская ходьба) - своеобразный вид любительского спорта, представляющий собой пешие путешествия, во время которых при ходьбе опираются на специальные палки, вид которых отдаленно напоминает лыжны