451 research outputs found
Dynamics of allosteric transitions in GroEL
The chaperonin GroEL-GroES, a machine which helps some proteins to fold,
cycles through a number of allosteric states, the state, with high affinity
for substrate proteins (SPs), the ATP-bound state, and the
() complex. Structures are known for each
of these states. Here, we use a self-organized polymer (SOP) model for the
GroEL allosteric states and a general structure-based technique to simulate the
dynamics of allosteric transitions in two subunits of GroEL and the heptamer.
The transition, in which the apical domains undergo counter-clockwise
motion, is mediated by a multiple salt-bridge switch mechanism, in which a
series of salt-bridges break and form. The initial event in the transition, during which GroEL rotates clockwise, involves a
spectacular outside-in movement of helices K and L that results in K80-D359
salt-bridge formation. In both the transitions there is considerable
heterogeneity in the transition pathways. The transition state ensembles (TSEs)
connecting the , , and states are broad with the the
TSE for the transition being more plastic than the TSE. The results suggest that GroEL functions as a
force-transmitting device in which forces of about (5-30) pN may act on the SP
during the reaction cycle.Comment: 32 pages, 10 figures (Longer version than the one published
Tunneling broadening of vibrational sidebands in molecular transistors
Transport through molecular quantum dots coupled to a single vibration mode
is studied in the case with strong coupling to the leads. We use an expansion
in the correlation between electrons on the molecule and electrons in the leads
and show that the tunneling broadening is strongly suppressed by the
combination of the Pauli principle and the quantization of the oscillator. As a
consequence the first Frank-Condon step is sharper than the higher order ones,
and its width, when compared to the bare tunneling strength, is reduced by the
overlap between the groundstates of the displaced and the non-displaced
oscillator.Comment: 8 pages, 3 figures. PRB, in pres
A transitional fossil mite (Astigmata: Levantoglyphidae fam. n.) from the early Cretaceous suggests gradual evolution of phoresy-related metamorphosis
Abstract Metamorphosis is a key innovation allowing the same species to inhabit different environments and accomplish different functions, leading to evolutionary success in many animal groups. Astigmata is a megadiverse lineage of mites that expanded into a great number of habitats via associations with invertebrate and vertebrate hosts (human associates include stored food mites, house dust mites, and scabies). The evolutionary success of Astigmata is linked to phoresy-related metamorphosis, namely the origin of the heteromorphic deutonymph, which is highly specialized for phoresy (dispersal on hosts). The origin of this instar is enigmatic since it is morphologically divergent and no intermediate forms are known. Here we describe the heteromorphic deutonymph of Levantoglyphus sidorchukae n. gen. and sp. (Levantoglyphidae fam. n.) from early Cretaceous amber of Lebanon (129 Ma), which displays a transitional morphology. It is similar to extant phoretic deutonymphs in its modifications for phoresy but has the masticatory system and other parts of the gnathosoma well-developed. These aspects point to a gradual evolution of the astigmatid heteromorphic morphology and metamorphosis. The presence of well-developed presumably host-seeking sensory elements on the gnathosoma suggests that the deutonymph was not feeding either during phoretic or pre- or postphoretic periods
Requirement of RIZ1 for cancer prevention by methyl-balanced diet
The typical Western diet is not balanced in methyl nutrients that regulate the level of the methyl donor S-adenosylmethionine (SAM) and its derivative metabolite S-adenosylhomocysteine (SAH), which in turn may control the activity of certain methyltransferases. Feeding rodents with amino acid defined and methyl-imbalanced diet decreases hepatic SAM and causes liver cancers. RIZ1 (PRDM2 or KMT8) is a tumor suppressor and functions in transcriptional repression by methylating histone H3 lysine 9. Here we show that a methyl-balanced diet conferred additional survival benefits compared to a tumor-inducing methyl-imbalanced diet only in mice with wild type RIZ1 but not in mice deficient in RIZ1. While absence of RIZ1 was tumorigenic in mice fed the balanced diet, its presence did not prevent tumor formation in mice fed the imbalanced diet. Unlike most of its related enzymes, RIZ1 was upregulated by methyl-balanced diet. Methyl-balanced diet did not fully repress oncogenes such as c-Jun in the absence of RIZ1. The data identify RIZ1 as a critical target of methyl-balanced diet in cancer prevention. The molecular understanding of dietary carcinogenesis may help people make informed choices on diet, which may greatly reduce the incidence of cancer
Spin states of the first four holes in a silicon nanowire quantum dot
We report measurements on a silicon nanowire quantum dot with a clarity that
allows for a complete understanding of the spin states of the first four holes.
First, we show control of the hole number down to one. Detailed measurements at
perpendicular magnetic fields reveal the Zeeman splitting of a single hole in
silicon. We are able to determine the ground-state spin configuration for one
to four holes occupying the quantum dot and find a spin filling with
alternating spin-down and spin-up holes, which is confirmed by
magnetospectroscopy up to 9T. Additionally, a so far inexplicable feature in
single-charge quantum dots in many materials systems is analyzed in detail. We
observe excitations of the zero-hole ground-state energy of the quantum dot,
which cannot correspond to electronic or Zeeman states. We show that the most
likely explanation is acoustic phonon emission to a cavity between the two
contacts to the nanowire.Comment: 24 pages, 8 figures, both including supporting informatio
Photon-Phonon-assisted tunneling through a single-molecular quantum dot
Based on exactly mapping of a many-body electron-phonon interaction problem
onto a one-body problem, we apply the well-established nonequilibrium Green
function technique to solve the time-dependent phonon-assisted tunneling at low
temperature through a single-molecular quantum dot connected to two leads,
which is subject to a microwave irradiation field. It is found that in the
presence of the electron-phonon interaction and the microwave irradiation
field, the time-average transmission and the nonlinear differential conductance
display additional peaks due to pure photon absorption or emission processes
and photon-absorption-assisted phonon emission processes. The variation of the
time-average current with frequency of the microwave irradiation field is also
studied.Comment: 9 pages, 6 figures, submitted to Phys. Rev. B. accepted by Phys. Rev.
Theory of Vibrationally Inelastic Electron Transport through Molecular Bridges
Vibrationally inelastic electron transport through a molecular bridge that is
connected to two leads is investigated. The study is based on a generic model
of vibrational excitation in resonant transmission of electrons through a
molecular junction. Employing methods from electron-molecule scattering theory,
the transmittance through the molecular bridge can be evaluated numerically
exactly. The current through the junction is obtained approximately using a
Landauer-type formula. Considering different parameter regimes, which include
both the case of a molecular bridge that is weakly coupled to the leads,
resulting in narrow resonance structures, and the opposite case of a broad
resonance caused by strong interaction with the leads, we investigate the
characteristic effects of coherent and dissipative vibrational motion on the
electron transport. Furthermore, the validity of widely used approximations
such as the wide-band approximation and the restriction to elastic transport
mechanisms is investigated in some detail.Comment: Submited to PRB, revised version according to comments of referees
(minor text changes and new citations
Vibrational Excitations in Weakly Coupled Single-Molecule Junctions: A Computational Analysis
In bulk systems, molecules are routinely identified by their vibrational
spectrum using Raman or infrared spectroscopy. In recent years, vibrational
excitation lines have been observed in low-temperature conductance measurements
on single molecule junctions and they can provide a similar means of
identification. We present a method to efficiently calculate these excitation
lines in weakly coupled, gateable single-molecule junctions, using a
combination of ab initio density functional theory and rate equations. Our
method takes transitions from excited to excited vibrational state into account
by evaluating the Franck-Condon factors for an arbitrary number of vibrational
quanta, and is therefore able to predict qualitatively different behaviour from
calculations limited to transitions from ground state to excited vibrational
state. We find that the vibrational spectrum is sensitive to the molecular
contact geometry and the charge state, and that it is generally necessary to
take more than one vibrational quantum into account. Quantitative comparison to
previously reported measurements on pi-conjugated molecules reveals that our
method is able to characterize the vibrational excitations and can be used to
identify single molecules in a junction. The method is computationally feasible
on commodity hardware.Comment: 9 pages, 7 figure
Lysosome-mediated processing of chromatin in senescence
Cellular senescence is a stable proliferation arrest, a potent tumor suppressor mechanism, and a likely contributor to tissue aging. Cellular senescence involves extensive cellular remodeling, including of chromatin structure. Autophagy and lysosomes are important for recycling of cellular constituents and cell remodeling. Here we show that an autophagy/lysosomal pathway processes chromatin in senescent cells. In senescent cells, lamin A/C–negative, but strongly γ-H2AX–positive and H3K27me3-positive, cytoplasmic chromatin fragments (CCFs) budded off nuclei, and this was associated with lamin B1 down-regulation and the loss of nuclear envelope integrity. In the cytoplasm, CCFs were targeted by the autophagy machinery. Senescent cells exhibited markers of lysosomal-mediated proteolytic processing of histones and were progressively depleted of total histone content in a lysosome-dependent manner. In vivo, depletion of histones correlated with nevus maturation, an established histopathologic parameter associated with proliferation arrest and clinical benignancy. We conclude that senescent cells process their chromatin via an autophagy/lysosomal pathway and that this might contribute to stability of senescence and tumor suppression
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