Molecular mechanism of the Escherichia coli AhpC in the function of a chaperone under heat-shock conditions

Published date : 20 Sep 2018

Peroxiredoxins (Prxs) are ubiquitous antioxidants utilizing a reactive cysteine for peroxide reduction and acting as a molecular chaperone under various stress conditions. Besides other stimulating factors, oxidative- and heat stress conditions trigger their ATP-independent chaperoning function. So far, many studies were intended to reveal the chaperoning mechanisms of the so-called sensitive Prxs of eukaryotes, which are susceptible to inactivation by over-oxidation of its reactive cysteine during H2O2 reduction.

type
Journal Paper
journal
Scientific Reports 8, No. 14151, 2018, doi: 10.1038/s41598-018-32527-7
Impact Factor
4.122

Single-molecule studies of flavivirus envelope dynamics: Experiment and computation

Published date : 14 Sep 2018

Flaviviruses are simple enveloped viruses exhibiting complex structural and functional heterogeneities. Decades of research have provided crucial basic insights, antiviral medication and moderately successful gene therapy trials. The most infectious particle is, however, not always the most abundant one in a population, questioning the utility of classic ensemble-averaging virology approaches. Indeed, viral replication is often not particularly efficient, prone to errors or containing parallel routes.

type
Journal Paper
journal
Progress in Biophysics and Molecular Biology, 2018, Sep 14, doi: 10.1016/j.pbiomolbio.2018.09.001
Impact Factor
3.427

Identification of FDA-approved drugs as novel allosteric inhibitors of human executioner caspases

Published date : 14 Sep 2018

The regulation of apoptosis is a tightly-coordinated process and caspases are its chief regulators. Of special importance are the executioner caspases, caspase-3/7, the activation of which irreversibly sets the cell on the path of death. Dysregulation of apoptosis, particularly an increased rate of cell death lies at the root of numerous human diseases. Although several peptide-based inhibitors targeting the homologous active site region of caspases have been developed, owing to their non-specific activity and poor pharmacological properties their use has largely been restricted.

type
Journal Paper
journal
Proteins: Structure, Function and Bioinformatics, 2018 Sep 8. doi: 10.1002/prot.25601
Impact Factor
2.274

Structures of the Human PGD2 Receptor CRTH2 Reveal Novel Mechanisms for Ligand Recognition

Published date : 13 Sep 2018

The signaling of prostaglandin D 2 (PGD 2) through G-protein-coupled receptor (GPCR) CRTH2 is a major pathway in type 2 inflammation. Compelling evidence suggests the therapeutic benefits of blocking CRTH2 signaling in many inflammatory disorders. Currently, a number of CRTH2 antagonists are under clinical investigation, and one compound, fevipiprant, has advanced to phase 3 clinical trials for asthma. Here, we present the crystal structures of human CRTH2 with two antagonists, fevipiprant and CAY10471.

type
Journal Paper
journal
Molecular Cell, 2018, doi: 10.1016/j.molcel.2018.08.009
Impact Factor
14.428

Integrated Multimodal Evaluation of Genotoxicity in ZFN-Modified Primary Human Cells

Published date : 29 Aug 2018

Iatrogenic adverse events in clinical trials of retroviral vector-mediated gene-corrected cells have prioritized the urgent need for more comprehensive and stringent assessment of potentially genotoxic off-target alterations and the biosafety of cells intended for therapeutic applications. Genome editing tools such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced palindromic repeats (CRISPR)-Cas9 nuclease systems are being investigated as safer and efficient alternatives for site-directed genome modification.

type
Book/Book Chapter
journal
Methods in Molecular Biology: Zinc Finger Proteins, 2018;1867:141-164. doi: 10.1007/978-1-4939-8799-3_11

Structural basis for endotoxin neutralisation and anti-inflammatory activity of thrombin-derived C-terminal peptides

Published date : 17 Aug 2018

Thrombin-derived C-terminal peptides (TCPs) of about 2 kDa are present in wounds, where they exert anti-endotoxic functions. Employing a combination of nuclear magnetic resonance spectroscopy (NMR), biophysical, mass spectrometry and cellular studies combined with in silico multiscale modelling, we here determine the bound conformation of HVF18 (HVFRLKKWIQKVIDQFGE), a TCP generated by neutrophil elastase, in complex with bacterial lipopolysaccharide (LPS) and define a previously undisclosed interaction between TCPs and human CD14.

type
Journal Paper
journal
Nature Communications, 2018 Jul 17;9(1):2762. doi: 10.1038/s41467-018-05242-0
Impact Factor
12.353

Conformational Transitions of Melittin between Aqueous and Lipid Phases: Comparison of Simulations with Experiments

Published date : 16 Aug 2018

Peptides are promising drug candidates with advantageous therapeutic properties. However, their inherent flexibility makes the development of structure−activity relationships difficult. Molecular dynamics simulations have been widely used to study peptide conformations, but they are limited by force field parameters.

type
Journal Paper
journal
The Journal of Physical Chemistry B, 2018, doi: 10.1021/acs.jpcb.8b06781
Impact Factor
3.146

Ultra-High Signal Detection of Human Embryonic Stem Cells Driven by Two-Dimensional Materials

Published date : 08 Aug 2018

We observed a unique bioelectric signal of human embryonic stem cells using direct current−voltage measurements facilitated by few-layered 2DMoS2 sheets. A 1.828 mA cell signal was achieved (2 orders of magnitude higher than previous electrical-based detection methods) as well as multiple cell reading cycles demonstrating I ∼ 1.9 mA. Native stem cell proliferation, viability, and pluripotency were preserved. Molecular dynamics simulations elucidated the origin of the 2D-MoS2 sheet-assisted increase in current flow.

type
Journal Paper
journal
ACS Applied Bio Materials, 2018, 1, Pg 210-215, doi: 10.1021/acsabm.8b00085.

Single mutations in the ε subunit from thermophilic Bacillus PS3 generate a high binding affinity site for ATP

Published date : 02 Aug 2018

The ε subunit from ATP synthases acts as an ATP sensor in the bacterial cell to prevent ATP hydrolysis and thus the waste of ATP under conditions of low ATP concentration. However, the ATP binding affinities from various bacterial organisms differ markedly, over several orders of magnitude. For example, the ATP synthases from thermophilic Bacillus PS3 and Escherichia coli exhibit affinities of 4 µM and 22 mM, respectively.

type
Journal Paper
journal
PeerJ 2018, Sep 5, doi: 10.7717/peerj.5505
Impact Factor
2.118

Anisotropic traction stresses and focal adhesion polarization mediates topography-induced cell elongation

Published date : 30 Jul 2018

Cell elongation and differentiation has been shown to be modulated by topographical cues provided by grating substratum. However, little is known about the mechanisms and forces involved in the grating-induced cell elongation, due to the difficulty in fabricating soft elastic gels that allow 3-dimensional (3D) cell traction stress measurements. In this paper, we present a method to fabricate soft elastic polyacrylamide grating substrates, using an imprinted polyethylene terephthalate mould, for 3D cell traction stress measurements.

type
Journal Paper
journal
Biomaterials, Vol. 181, October 2018, Pg 103-112, doi: 10.1016/j.biomaterials.2018.07.057
Impact Factor
8.806