Search results for "Meri"
showing 10 items of 7596 documents
The malate sensing two-component system MaeKR is a non-canonical class of sensory complex for C4-dicarboxylates
2017
16 páginas, 7 figuras, 2 tablas
A Janus-Faced IM30 Ring Involved in Thylakoid Membrane Fusion Is Assembled from IM30 Tetramers.
2017
Summary Biogenesis and dynamics of thylakoid membranes likely involves membrane fusion events. Membrane attachment of the inner membrane-associated protein of 30 kDa (IM30) affects the structure of the lipid bilayer, finally resulting in membrane fusion. Yet, how IM30 triggers membrane fusion is largely unclear. IM30 monomers pre-assemble into stable tetrameric building blocks, which further align to form oligomeric ring structures, and differently sized IM30 rings bind to membranes. Based on a 3D reconstruction of IM30 rings, we locate the IM30 loop 2 region at the bottom of the ring and show intact membrane binding but missing fusogenic activity of loop 2 mutants. However, helix 7, which …
High-Pressure-Driven Reversible Dissociation of α-Synuclein Fibrils Reveals Structural Hierarchy
2017
The analysis of the α-synuclein (aS) aggregation process, which is involved in Parkinson's disease etiopathogenesis, and of the structural feature of the resulting amyloid fibrils may shed light on the relationship between the structure of aS aggregates and their toxicity. This may be considered a paradigm of the ground work needed to tackle the molecular basis of all the protein-aggregation-related diseases. With this aim, we used chemical and physical dissociation methods to explore the structural organization of wild-type aS fibrils. High pressure (in the kbar range) and alkaline pH were used to disassemble fibrils to collect information on the hierarchic pathway by which distinct β-sh…
The dimer-monomer equilibrium of SARS-CoV-2 main protease is affected by small molecule inhibitors
2021
AbstractThe maturation of coronavirus SARS-CoV-2, which is the etiological agent at the origin of the COVID-19 pandemic, requires a main protease Mpro to cleave the virus-encoded polyproteins. Despite a wealth of experimental information already available, there is wide disagreement about the Mpro monomer-dimer equilibrium dissociation constant. Since the functional unit of Mpro is a homodimer, the detailed knowledge of the thermodynamics of this equilibrium is a key piece of information for possible therapeutic intervention, with small molecules interfering with dimerization being potential broad-spectrum antiviral drug leads. In the present study, we exploit Small Angle X-ray Scattering (…
Bax transmembrane domain interacts with prosurvival Bcl-2 proteins in biological membranes
2016
The Bcl-2 (B-cell lymphoma 2) protein Bax (Bcl-2 associated X, apoptosis regulator) can commit cells to apoptosis via outer mitochondrial membrane permeabilization. Bax activity is controlled in healthy cells by prosurvival Bcl-2 proteins. C-terminal Bax transmembrane domain interactions were implicated recently in Bax pore formation. Here, we show that the isolated transmembrane domains of Bax, Bcl-xL (B-cell lymphoma-extra large), and Bcl-2 can mediate interactions between Bax and prosurvival proteins inside the membrane in the absence of apoptotic stimuli. Bcl-2 protein transmembrane domains specifically homooligomerize and heterooligomerize in bacterial and mitochondrial membranes. Thei…
Septin/anillin filaments scaffold central nervous system myelin to accelerate nerve conduction
2016
Myelination of axons facilitates rapid impulse propagation in the nervous system. The axon/myelin-unit becomes impaired in myelin-related disorders and upon normal aging. However, the molecular cause of many pathological features, including the frequently observed myelin outfoldings, remained unknown. Using label-free quantitative proteomics, we find that the presence of myelin outfoldings correlates with a loss of cytoskeletal septins in myelin. Regulated by phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2)-levels, myelin septins (SEPT2/SEPT4/SEPT7/SEPT8) and the PI(4,5)P2-adaptor anillin form previously unrecognized filaments that extend longitudinally along myelinated axons. By confoca…
Genetically elevated gamma-glutamyltransferase and Alzheimer's disease
2018
Observational epidemiological evidence supports a linear and independent association between serum gamma-glutamyltransferase (GGT) concentrations and the risk of Alzheimer's disease (AD). However, the causality of this association has not been previously investigated. We sought to assess the causal nature of this association using a Mendelian randomization (MR) approach. Using inverse-variance weighted MR analysis, we assessed the association between GGT and AD using summary statistics for single nucleotide polymorphism (SNP)-AD associations obtained from the International Genomics of Alzheimer's Project of 17,008 individuals with AD and 37,154 controls. We used 26 SNPs significantly associ…
Three-dimensional multiple-particle tracking with nanometric precision over tunable axial ranges
2017
The precise localization of nanometric objects in three dimensions is essential to identify functional diffusion mechanisms in complex systems at the cellular or molecular level. However, most optical methods can achieve high temporal resolution and high localization precision only in two dimensions or over a limited axial (z) range. Here we develop a novel wide-field detection system based on an electrically tunable lens that can track multiple individual nanoscale emitters in three dimensions over a tunable axial range with nanometric localization precision. The optical principle of the technique is based on the simultaneous acquisition of two images with an extended depth of field while …
Distribution of Interstitial Telomeric Sequences in Primates and the Pygmy Tree Shrew (Scandentia).
2017
It has been hypothesized that interstitial telomeric sequences (ITSs), i.e., repeated telomeric DNA sequences found at intrachromosomal sites in many vertebrates, could be correlated to chromosomal rearrangements and plasticity. To test this hypothesis, we hybridized a telomeric PNA probe through FISH on representative species of 2 primate infraorders, Strepsirrhini (<i>Lemur catta, Otolemur garnettii, Nycticebus coucang</i>) and Catarrhini (<i>Erythrocebus patas, Cercopithecus petaurista, Chlorocebus aethiops, Colobus guereza</i>), as well as on 1 species of the order Scandentia, <i>Tupaia minor</i>, used as an outgroup for primates in phylogenetic recon…
Femtosecond structural dynamics drives the trans/cis isomerization in photoactive yellow protein
2016
Many biological processes depend on detecting and responding to light. The response is often mediated by a structural change in a protein that begins when absorption of a photon causes isomerization of a chromophore bound to the protein. Pande et al. used x-ray pulses emitted by a free electron laser source to conduct time-resolved serial femtosecond crystallography in the time range of 100 fs to 3 ms. This allowed for the real-time tracking of the trans-cis isomerization of the chromophore in photoactive yellow protein and the associated structural changes in the protein.Science, this issue p. 725A variety of organisms have evolved mechanisms to detect and respond to light, in which the re…