scholarly journals Structure and function of the bacterial protein toxin phenomycin

2019 ◽  
Author(s):  
Bente K. Hansen ◽  
Camilla K. Larsen ◽  
Jacob T. Nielsen ◽  
Esben B. Svenningsen ◽  
Lan B. Van ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Endosomal Escape ◽  
Bacterial Protein ◽  
Direct Inhibition ◽  
Uptake Mechanism ◽  
Protein Toxin ◽  
Limiting Step ◽  
High Resolution Structure ◽  
And Function ◽  
Resolution Structure

SummaryPhenomycin is a bacterial mini-protein of 89 amino acids discovered more than 50 years ago with toxicity in the nanomolar regime towards mammalian cells. The protein inhibits the function of the eukaryotic ribosome in cell free systems and appears to target translation initiation. Several fundamental questions concerning the cellular activity of phenomycin have however remained unanswered. In this paper, we have used morphological profiling to show that direct inhibition of translation underlies the toxicity of phenomycin in cells. We have performed studies of the cellular uptake mechanism of phenomycin, showing that endosomal escape is the toxicity-limiting step, and we have solved a solution phase high-resolution structure of the protein using NMR spectroscopy. Through bioinformatic as well as functional comparisons between phenomycin and two homologs, we have identified a peptide segment, which constitutes one of two loops in the structure, that is critical for the toxicity of phenomycin.

The ryanodine receptor provides high throughput Ca2+-release but is precisely regulated by networks of associated proteins: a focus on proteins relevant to phosphorylation

2015 ◽  
Vol 43 (3) ◽  
pp. 426-433 ◽  
Author(s):  
Fiona O'Brien ◽  
Elisa Venturi ◽  
Rebecca Sitsapesan
Keyword(s):  
Spatial Organization ◽  
Ryanodine Receptors ◽  
Integrated System ◽  
Fine Tuning ◽  
Control Mechanisms ◽  
Fk 506 ◽  
High Resolution Structure ◽  
Associated Proteins ◽  
And Function ◽  
Resolution Structure

Once opened, ryanodine receptors (RyR) are efficient pathways for the release of Ca2+ from the endoplasmic/sarcoplasmic reticulum (ER/SR). The precise nature of the Ca2+-release event, however, requires fine-tuning for the specific process and type of cell involved. For example, the spatial organization of RyRs, the luminal [Ca2+] and the influence of soluble regulators that fluctuate under physiological and pathophysiological control mechanisms, all affect the amplitude and duration of RyR Ca2+ fluxes. Various proteins are docked tightly to the huge bulky structure of RyR and there is growing evidence that, together, they provide a sophisticated and integrated system for regulating RyR channel gating. This review focuses on those proteins that are relevant to phosphorylation of RyR channels with particular reference to the cardiac isoform of RyR (RyR2). How phosphorylation of RyR affects channel activity and whether proteins such as the FK-506 binding proteins (FKBP12 and FKBP12.6) are involved, have been highly controversial subjects for more than a decade. But that is expected given the large number of participating proteins, the relevance of phosphorylation in heart failure and inherited arrhythmic diseases, and the frustrations of predicting relationships between structure and function before the advent of a high resolution structure of RyR.

scholarly journals GeRelion: GPU-enhanced parallel implementation of single particle cryo-EM image processing

2016 ◽  
Author(s):  
Huayou Su ◽  
Wen Wen ◽  
Xiaoli Du ◽  
Xicheng Lu ◽  
Maofu Liao ◽  
...  
Keyword(s):  
Image Processing ◽  
Single Particle ◽  
Parallel Implementation ◽  
Data Sets ◽  
Structural Details ◽  
High Resolution Structure ◽  
Molecular Machinery ◽  
Speed Up ◽  
And Function ◽  
Resolution Structure

Single particle cryo-EM emerges as a powerful and versatile method to characterize the structure and function of macromolecules, revealing the structural details of critical molecular machinery inside the cells. RELION is a widely used EM image processing software, and most of the recently published single particle cryo-EM structures were generated by using RELION. Due to the massive computational loads and the growing demands for processing much larger cryo-EM data sets, there is a pressing need to speed up image processing. Here we present GeRelion (https://github.com/gpu-pdl¬nudt/GeRelion), an efficient parallel implementation of RELION on GPU system. In the performance tests using two cryo-EM data sets, GeRelion on 4 or 8 GPU cards outperformed RELION on 256 CPU cores, demonstrating dramatically improved speed and superb scalability. By greatly accelerating single particle cryo-EM structural analysis, GeRelion will facilitate both high resolution structure determination and dissection of mixed conformations of dynamic molecular machines.

scholarly journals Cryo-EM structure of Mycobacterium smegmatis DyP-loaded encapsulin

2021 ◽  
Vol 118 (16) ◽  
pp. e2025658118
Author(s):  
Yanting Tang ◽  
An Mu ◽  
Yuying Zhang ◽  
Shan Zhou ◽  
Weiwei Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mycobacterium Smegmatis ◽  
Structural Features ◽  
Antituberculosis Drug ◽  
Potential Mechanism ◽  
Cargo Protein ◽  
High Resolution Structure ◽  
Axis Of Symmetry ◽  
And Function ◽  
Resolution Structure

Encapsulins containing dye-decolorizing peroxidase (DyP)-type peroxidases are ubiquitous among prokaryotes, protecting cells against oxidative stress. However, little is known about how they interact and function. Here, we have isolated a native cargo-packaging encapsulin from Mycobacterium smegmatis and determined its complete high-resolution structure by cryogenic electron microscopy (cryo-EM). This encapsulin comprises an icosahedral shell and a dodecameric DyP cargo. The dodecameric DyP consists of two hexamers with a twofold axis of symmetry and stretches across the interior of the encapsulin. Our results reveal that the encapsulin shell plays a role in stabilizing the dodecameric DyP. Furthermore, we have proposed a potential mechanism for removing the hydrogen peroxide based on the structural features. Our study also suggests that the DyP is the primary cargo protein of mycobacterial encapsulins and is a potential target for antituberculosis drug discovery.

scholarly journals Structure and Function of the Bacterial Protein Toxin Phenomycin

Structure ◽  
2020 ◽  
Vol 28 (5) ◽  
pp. 528-539.e9 ◽  
Author(s):  
Bente K. Hansen ◽  
Camilla K. Larsen ◽  
Jakob T. Nielsen ◽  
Esben B. Svenningsen ◽  
Lan B. Van ◽  
...  
Keyword(s):  
Structure And Function ◽  
Bacterial Protein ◽  
Protein Toxin ◽  
And Function

Towards understanding the catalytic core structure of the spliceosome

2005 ◽  
Vol 33 (3) ◽  
pp. 447-449 ◽  
Author(s):  
S.E. Butcher ◽  
D.A. Brow
Keyword(s):  
Structure And Function ◽  
Mrna Splicing ◽  
Catalytic Core ◽  
Coding Regions ◽  
High Resolution Structure ◽  
Associated Proteins ◽  
And Function ◽  
Mrna Precursor ◽  
Precursor Mrna ◽  
Resolution Structure

The spliceosome catalyses the splicing of nuclear pre-mRNA (precursor mRNA) in eukaryotes. Pre-mRNA splicing is essential to remove internal non-coding regions of pre-mRNA (introns) and to join the remaining segments (exons) into mRNA before translation. The spliceosome is a complex assembly of five RNAs (U1, U2, U4, U5 and U6) and many dozens of associated proteins. Although a high-resolution structure of the spliceosome is not yet available, inroads have been made towards understanding its structure and function. There is growing evidence suggesting that U2 and U6 RNAs, of the five, may contribute to the catalysis of pre-mRNA splicing. In this review, recent progress towards understanding the structure and function of U2 and U6 RNAs is summarized.

scholarly journals Modelling the active SARS-CoV-2 helicase complex as a basis for structure-based inhibitor design

2020 ◽  
Author(s):  
Dénes Berta ◽  
Magd Badaoui ◽  
Pedro J. Buigues ◽  
Sam Alexander Martino ◽  
Andrei V. Pisliakov ◽  
...  
Keyword(s):  
Drug Target ◽  
Md Simulation ◽  
Structural Information ◽  
Rna Helicase ◽  
Atomic Level ◽  
Virus Rna ◽  
High Resolution Structure ◽  
And Function ◽  
Structural Insights ◽  
Resolution Structure

ABSTRACTHaving claimed over 1 million lives worldwide to date, the ongoing COVID-19 pandemic has created one of the biggest challenges to develop an effective drug to treat infected patients. Among all the proteins expressed by the virus, RNA helicase is a fundamental protein for viral replication, and it is highly conserved among the coronaviridae family. To date, there is no high-resolution structure of helicase bound with ATP and RNA. We present here structural insights and molecular dynamics (MD) simulation results of the SARS-CoV-2 RNA helicase both in its apo form and in complex with its natural substrates. Our structural information of the catalytically competent helicase complex provides valuable insights for the mechanism and function of this enzyme at the atomic level, a key to develop specific inhibitors for this potential COVID-19 drug target.

High-resolution structure determination by ALCHEMI

1983 ◽  
Vol 41 ◽  
pp. 178-181 ◽  
Author(s):  
Peter G. Self ◽  
Peter R. Buseck
Keyword(s):  
Site Occupancy ◽  
Real Space ◽  
Unit Cell ◽  
Bragg Angle ◽  
Electron Current ◽  
High Resolution Structure ◽  
Beam Incident ◽  
Crystallographic Planes ◽  
Electron Beam Incident ◽  
Resolution Structure

ALCHEMI (Atom Location by CHanneling Enhanced Microanalysis) enables the site occupancy of atoms in single crystals to be determined. In this article the fundamentals of the method for both EDS and EELS will be discussed. Unlike HRTEM, ALCHEMI does not place stringent resolution requirements on the microscope and, because EDS clearly distinguishes between elements of similar atomic number, it can offer some advantages over HRTEM. It does however, place certain constraints on the crystal. These constraints are: a) the sites of interest must lie on alternate crystallographic planes, b) the projected charge density on the alternate planes must be significantly different, and c) there must be at least one atomic species that lies solely on one of the planes.An electron beam incident on a crystal undergoes elastic scattering; in reciprocal space this is seen as a diffraction pattern and in real space this is a modulation of the electron current across the unit cell. When diffraction is strong (i.e., when the crystal is oriented near to the Bragg angle of a low-order reflection) the electron current at one point in the unit cell will differ significantly from that at another point.

Cathodoluminescence of Catalyst Crystallites

1982 ◽  
Vol 40 ◽  
pp. 664-665
Author(s):  
E.D. Boyes ◽  
P.L. Gai ◽  
D.B. Darby ◽  
C. Warwick
Keyword(s):  
Defect Density ◽  
Chemical Properties ◽  
Operating Conditions ◽  
Semiconductor Materials ◽  
Environmental Cell ◽  
High Resolution Structure ◽  
Commercially Important ◽  
Crystallographic Defects ◽  
Resolution Structure

The extended crystallographic defects introduced into some oxide catalysts under operating conditions may be a consequence and accommodation of the changes produced by the catalytic activity, rather than always being the origin of the reactivity. Operation without such defects has been established for the commercially important tellurium molybdate system. in addition it is clear that the point defect density and the electronic structure can both have a significant influence on the chemical properties and hence on the effectiveness (activity and selectivity) of the material as a catalyst. SEM/probe techniques more commonly applied to semiconductor materials, have been investigated to supplement the information obtained from in-situ environmental cell HVEM, ultra-high resolution structure imaging and more conventional AEM and EPMA chemical microanalysis.

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