A molecular mechanism of chaperone–client recognition

Molecular chaperones are essential in aiding client proteins to fold into their native structure and in maintaining cellular protein homeostasis. However, mechanistic aspects of chaperone function are still not well understood at the atomic level. We use nuclear magnetic resonance spectroscopy to elucidate the mechanism underlying client recognition by the adenosine triphosphate-independent chaperone Spy at the atomic level and derive a structural model for the chaperone-client complex. Spy interacts with its partially folded client Im7 by selective recognition of flexible, locally frustrated regions in a dynamic fashion. The interaction with Spy destabilizes a partially folded client but spatially compacts an unfolded client conformational ensemble. By increasing client backbone dynamics, the chaperone facilitates the search for the native structure. A comparison of the interaction of Im7 with two other chaperones suggests that the underlying principle of recognizing frustrated segments is of a fundamental nature

Coplanar Waveguide-Fed Broadband Microwave Devices with (or without) a Thin Dielectric Substrate for Use in Flexible Electronic Systems

Two examples of microwave devices, fed by a coplanar waveguide and realized on a thin substrate (or without such a substrate), are employed to investigate the influence of devices’ curvatures and the proximity of different materials on their parameters. To perform the tests, a broadband antenna and a low-pass filter are chosen. A feeding coplanar waveguide is realized on a dielectric material brick attached to an SMA connector and the main device structure is placed in the air or on a thin substrate. The utilization of a thin substrate or its removal from the structure gives rise to the possibility of placing the devices on curved surfaces. The investigated devices are redesigned and manufactured. The antenna has a total size of 46 mm × 44 mm and covers a frequency range of 2.4–35 GHz which gives a 174% fractional bandwidth. The filter has a total size of 50 mm × 80 mm and its bandwidth has a cutoff frequency of 3.4 GHz. The obtained results are verified by measurements and good agreement is achieved

Intrinsic regulation of FIC-domain AMP-transferases by oligomerization and automodification

Filamentation induced by cyclic AMP (FIC)-domain enzymes catalyze adenylylation or other posttranslational modifications of target proteins to control their function. Recently, we have shown that Fic enzymes are autoinhibited by an α-helix (αinh) that partly obstructs the active site. For the single-domain class III Fic proteins, the αinh is located at the C terminus and its deletion relieves autoinhibition. However, it has remained unclear how activation occurs naturally. Here, we show by structural, biophysical, and enzymatic analyses combined with in vivo data that the class III Fic protein NmFic from Neisseria meningitidis gets autoadenylylated in cis, thereby autonomously relieving autoinhibition and thus allowing subsequent adenylylation of its target, the DNA gyrase subunit GyrB. Furthermore, we show that NmFic activation is antagonized by tetramerization. The combination of autoadenylylation and tetramerization results in nonmonotonic concentration dependence of NmFic activity and a pronounced lag phase in the progress of target adenylylation. Bioinformatic analyses indicate that this elaborate dual-control mechanism is conserved throughout class III Fic proteins

The dynamic dimer structure of the chaperone Trigger Factor

The chaperone Trigger Factor (TF) from Escherichia coli forms a dimer at cellular concentrations. While the monomer structure of TF is well known, the spatial arrangement of this dimeric chaperone storage form has remained unclear. Here, we determine its structure by a combination of high-resolution NMR spectroscopy and biophysical methods. TF forms a symmetric head-to-tail dimer, where the ribosome binding domain is in contact with the substrate binding domain, while the peptidyl-prolyl isomerase domain contributes only slightly to the dimer affinity. The dimer structure is highly dynamic, with the two ribosome binding domains populating a conformational ensemble in the center. These dynamics result from intermolecular in trans interactions of the TF client-binding site with the ribosome binding domain, which is conformationally frustrated in the absence of the ribosome. The avidity in the dimer structure explains how the dimeric state of TF can be monomerized also by weakly interacting clients

On Security Management: Improving Energy Efficiency, Decreasing Negative Environmental Impact, and Reducing Financial Costs for Data Centers

Security management is one of the most significant issues in nowadays data centers. Selection of appropriate security mechanisms and effective energy consumption management together with caring for the environment enforces a profound analysis of the considered system. In this paper, we propose a specialized decision support system with a multilevel, comprehensive analysis scheme. As a result of the extensive use of mathematical methods and statistics, guidelines and indicators returned by the proposed approach facilitate the decision-making process and conserve decision-maker’s time and attention. In the paper we utilized proposed multilevel analysis scheme to manage security-based data flow in the example data center. Determining the most secure, energy-efficient, environmental friendly security mechanisms, we implemented the role-based access control method in Quality of Protection Modeling Language (QoP-ML) and evaluated its performance in terms of mentioned factors