318 research outputs found
Cryo-EM of ribosomal 80S complexes with termination factors reveals the translocated Cricket Paralysis Virus IRES
The cricket paralysis virus (CrPV) uses an internal ribosomal entry site (IRES) to hijack the ribosome. In a remarkable RNA-based mechanism involving neither initiation factor nor initiator tRNA, the CrPV IRES jumpstarts translation in the elongation phase from the ribosomal A site. Here, we present cryoelectron microscopy (cryo-EM) maps of 80S⋅CrPV-STOP ⋅ eRF1 ⋅ eRF3 ⋅ GMPPNP and 80S⋅CrPV-STOP ⋅ eRF1 complexes, revealing a previously unseen binding state of the IRES and directly rationalizing that an eEF2-dependent translocation of the IRES is required to allow the first A-site occupation. During this unusual translocation event, the IRES undergoes a pronounced conformational change to a more stretched conformation. At the same time, our structural analysis provides information about the binding modes of eRF1 ⋅ eRF3 ⋅ GMPPNP and eRF1 in a minimal system. It shows that neither eRF3 nor ABCE1 are required for the active conformation of eRF1 at the intersection between eukaryotic termination and recycling
Regulation of the mammalian elongation cycle by subunit rolling: a eukaryotic-specific ribosome rearrangement
The extent to which bacterial ribosomes and the significantly larger eukaryotic ribosomes share the same mechanisms of ribosomal elongation is unknown. Here, we present subnanometer resolution cryoelectron microscopy maps of the mammalian 80S ribosome in the posttranslocational state and in complex with the eukaryotic eEF1AVal-tRNAGMPPNP ternary complex, revealing significant differences in the elongation mechanism between bacteria and mammals. Surprisingly, and in contrast to bacterial ribosomes, a rotation of the small subunit around its long axis and orthogonal to the well-known intersubunit rotation distinguishes the posttranslocational state from the classical pretranslocational state ribosome. We term this motion "subunit rolling." Correspondingly, a mammalian decoding complex visualized in substates before and after codon recognition reveals structural distinctions from the bacterial system. These findings suggest how codon recognition leads to GTPase activation in the mammalian system and demonstrate that in mammalia subunit rolling occurs during tRNA selection
Transport Coefficients of the Yukawa One Component Plasma
We present equilibrium molecular-dynamics computations of the thermal
conductivity and the two viscosities of the Yukawa one-component plasma. The
simulations were performed within periodic boundary conditions and Ewald sums
were implemented for the potentials, the forces, and for all the currents which
enter the Kubo formulas. For large values of the screening parameter, our
estimates of the shear viscosity and the thermal conductivity are in good
agreement with the predictions of the Chapman-Enskog theory.Comment: 11 pages, 2 figure
QED can explain the non-thermal emission from SGRs and AXPs : Variability
Owing to effects arising from quantum electrodynamics (QED),
magnetohydrodynamical fast modes of sufficient strength will break down to form
electron-positron pairs while traversing the magnetospheres of strongly
magnetised neutron stars. The bulk of the energy of the fast mode fuels the
development of an electron-positron fireball. However, a small, but potentially
observable, fraction of the energy ( ergs) can generate a
non-thermal distribution of electrons and positrons far from the star. This
paper examines the cooling and radiative output of these particles. Small-scale
waves may produce only the non-thermal emission. The properties of this
non-thermal emission in the absence of a fireball match those of the quiescent,
non-thermal radiation recently observed non-thermal emission from several
anomalous X-ray pulsars and soft-gamma repeaters. Initial estimates of the
emission as a function of angle indicate that the non-thermal emission should
be beamed and therefore one would expect this emission to be pulsed as well.
According to this model the pulsation of the non-thermal emission should be
between 90 and 180 degrees out of phase from the thermal emission from the
stellar surface.Comment: 7 pages, 5 figures, to appear in the proceedings of the conference
"Isolated Neutron Stars: from the Interior to the Surface" (April 2006,
London), eds. D. Page, R. Turolla, & S. Zane, Astrophysics & Space Scienc
SMOG@ctbp: simplified deployment of structure-based models in GROMACS
Molecular dynamics simulations with coarse-grained and/or simplified Hamiltonians are an effective means of capturing the functionally important long-time and large-length scale motions of proteins and RNAs. Structure-based Hamiltonians, simplified models developed from the energy landscape theory of protein folding, have become a standard tool for investigating biomolecular dynamics. SMOG@ctbp is an effort to simplify the use of structure-based models. The purpose of the web server is two fold. First, the web tool simplifies the process of implementing a well-characterized structure-based model on a state-of-the-art, open source, molecular dynamics package, GROMACS. Second, the tutorial-like format helps speed the learning curve of those unfamiliar with molecular dynamics. A web tool user is able to upload any multi-chain biomolecular system consisting of standard RNA, DNA and amino acids in PDB format and receive as output all files necessary to implement the model in GROMACS. Both Cα and all-atom versions of the model are available. SMOG@ctbp resides at http://smog.ucsd.edu
VarySysDB: a human genetic polymorphism database based on all H-InvDB transcripts
Creation of a vast variety of proteins is accomplished by genetic variation and a variety of alternative splicing transcripts. Currently, however, the abundant available data on genetic variation and the transcriptome are stored independently and in a dispersed fashion. In order to provide a research resource regarding the effects of human genetic polymorphism on various transcripts, we developed VarySysDB, a genetic polymorphism database based on 187 156 extensively annotated matured mRNA transcripts from 36 073 loci provided by H-InvDB. VarySysDB offers information encompassing published human genetic polymorphisms for each of these transcripts separately. This allows comparisons of effects derived from a polymorphism on different transcripts. The published information we analyzed includes single nucleotide polymorphisms and deletion–insertion polymorphisms from dbSNP, copy number variations from Database of Genomic Variants, short tandem repeats and single amino acid repeats from H-InvDB and linkage disequilibrium regions from D-HaploDB. The information can be searched and retrieved by features, functions and effects of polymorphisms, as well as by keywords. VarySysDB combines two kinds of viewers, GBrowse and Sequence View, to facilitate understanding of the positional relationship among polymorphisms, genome, transcripts, loci and functional domains. We expect that VarySysDB will yield useful information on polymorphisms affecting gene expression and phenotypes. VarySysDB is available at http://h-invitational.jp/varygene/
Higher media multi-tasking activity is associated with smaller gray-matter density in the anterior cingulate cortex
Media multitasking, or the concurrent consumption of multiple media forms, is increasingly prevalent in today’s society and has been associated with negative psychosocial and cognitive impacts. Individuals who engage in heavier media-multitasking are found to perform worse on cognitive control tasks and exhibit more socio-emotional difficulties. However, the neural processes associated with media multi-tasking remain unexplored. The present study investigated relationships between media multitasking activity and brain structure. Research has demonstrated that brain structure can be altered upon prolonged exposure to novel environments and experience. Thus, we expected differential engagements in media multitasking to correlate with brain structure variability. This was confirmed via Voxel-Based Morphometry (VBM) analyses: Individuals with higher Media Multitasking Index (MMI) scores had smaller gray matter density in the anterior cingulate cortex (ACC). Functional connectivity between this ACC region and the precuneus was negatively associated with MMI. Our findings suggest a possible structural correlate for the observed decreased cognitive control performance and socio-emotional regulation in heavy media-multitaskers. While the cross-sectional nature of our study does not allow us to specify the direction of causality, our results brought to light novel associations between individual media multitasking behaviors and ACC structure differences
Thermal Density Functional Theory in Context
This chapter introduces thermal density functional theory, starting from the
ground-state theory and assuming a background in quantum mechanics and
statistical mechanics. We review the foundations of density functional theory
(DFT) by illustrating some of its key reformulations. The basics of DFT for
thermal ensembles are explained in this context, as are tools useful for
analysis and development of approximations. We close by discussing some key
ideas relating thermal DFT and the ground state. This review emphasizes thermal
DFT's strengths as a consistent and general framework.Comment: Submitted to Spring Verlag as chapter in "Computational Challenges in
Warm Dense Matter", F. Graziani et al. ed
Cryo-EM structure of the small subunit of the mammalian mitochondrial ribosome
The mitochondrial ribosome (mitoribosome) is a macromolecular complex that plays a central role in mitochondrial protein synthesis. Its small subunit is involved directly in the recruitment and decoding of mitochondrial mRNAs. Defects in mitochondrial translation, including mutations in components of the mitoribosome, are known to cause numerous human genetic diseases. Thus, knowledge of the molecular architecture of the mitoribosome is essential for a better understanding of those diseases and of the process of translation. To our knowledge, this article describes the first detailed cryo-EM structure of the small subunit of the mammalian mitoribosome. The study provides important clues about the evolution of this macromolecular complex and reveals unique structural features that could be important in the translation of the unusual mitochondrial mRNAs
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