Structural Insight into the Mechanism of PALB2 Interaction with MRG15

The tumor suppressor protein partner and localizer of BRCA2 (PALB2) orchestrates the interactions between breast cancer susceptibility proteins 1 and 2 (BRCA1, -2) that are critical for genome stability, homologous recombination (HR) and DNA repair. PALB2 mutations predispose patients to a spectrum of cancers, including breast and ovarian cancers. PALB2 localizes HR machinery to chromatin and links it with transcription through multiple DNA and protein interactions. This includes its interaction with MRG15 (Morf-related gene on chromosome 15), which is part of many transcription complexes, including the HAT-associated and the HDAC-associated complexes. This interaction is critical for PALB2 localization in actively transcribed genes, where transcription/replication conflicts lead to frequent replication stress and DNA breaks. We solved the crystal structure of the MRG15 MRG domain bound to the PALB2 peptide and investigated the effect of several PALB2 mutations, including patient-derived variants. PALB2 interacts with an extended surface of the MRG that is known to interact with other proteins. This, together with a nanomolar affinity, suggests that the binding of MRG15 partners, including PALB2, to this region is mutually exclusive. Breast cancer-related mutations of PALB2 cause only minor attenuation of the binding affinity. New data reveal the mechanism of PALB2-MRG15 binding, advancing our understanding of PALB2 function in chromosome maintenance and tumorigenesis.

Crystal structures and functional analysis of the ZnF5-WWE1-WWE2 region of PARP13/ZAP define a new mode of engaging poly(ADP-ribose)

PARP13/ZAP acts against multiple viruses through recognizing and promoting degradation of cytoplasmic viral mRNA. PARP13 has four N-terminal Zn-finger motifs that bind CG-rich nucleotide sequences, and a C-terminal ADP ribosyltransferase fold similar to other PARPs. A central region predicted to contain a fifth Zn-finger and two tandem WWE domains is implicated in binding poly(ADP-ribose); however, there are limited insights into the structure and function of this PARP13 region (ZnF5-WWE1-WWE2). Here, we present crystal structures of ZnF5-WWE1-WWE2 from mouse PARP13 in complex with ADP-ribose and with ATP. ZnF5-WWE1-WWE2 crystallized as a dimer with major contacts formed between WWE1 and WWE2 originating from different monomers, indicative of a more compact monomeric arrangement of the tandem WWE domains. Solution scattering experiments and biophysical analysis indicated a monomer in solution, suggesting that the crystal dimer represents domain swapping that could potentially represent a PARP13 conformation assumed when signaling viral RNA detection. The crystal structure and binding studies demonstrate that WWE2 interacts with ADP-ribose and ATP, whereas WWE1 does not have a functional binding site. The shape of the WWE2 binding pocket disfavors interaction with the ribose-ribose linkage of poly(ADP-ribose). Binding studies with poly(ADP-ribose) ligands indicate that WWE2 serves as an anchor for preferential binding to the terminal end of poly(ADP-ribose), and the composite structure of ZnF5-WWE1-WWE2 forms an extended surface to engage polymer chains of ADP-ribose. This model represents a novel mode of poly(ADP-ribose) recognition and provides a structural framework for investigating poly(ADP-ribose) impact on PARP13 function.

A brief comparative examination of tangent hyperbolic hybrid nanofluid through a extending surface: numerical Keller–Box scheme

A novel hybrid nanofluid was explored in order to find an efficient heat-transmitting fluid to replace standard fluids and revolutionary nanofluids. By using tangent hyperbolic hybrid combination nanoliquid with non-Newtonian ethylene glycol (EG) as a basis fluid and a copper (Cu) and titanium dioxide (TiO2) mixture, this work aims to investigate the viscoelastic elements of the thermal transferring process. Flow and thermal facts, such as a slippery extended surface with magnetohydrodynamic (MHD), suction/injection, form factor, Joule heating, and thermal radiation effects, including changing thermal conductivity, were also integrated. The Keller–Box method was used to perform collective numerical computations of parametric analysis using governing equivalences. In the form of graphs and tables, the results of TiO2–Cu/EG hybrid nanofluid were compared to those of standard Cu/EG nanofluid in important critical physical circumstances. The entropy generation study was used to examine energy balance and usefulness for important physically impacting parameters. Detailed scrutiny on entropy development get assisted with Weissenberg number, magnetic parameter, fractional volumes, injection parameter, thermal radiation, variable thermal conductivity, Biot number, shape variation parameter, Reynolds and Brinkman number. Whereas the entropy gets resisted for slip and suction parameter. In this case, spotted entropy buildup with important parametric ranges could aid future optimization.

Ultrasonic Exposure of the Liquid Film for Highly Efficient Gas Absorption

A model of ultrasonic intensification of the absorption process is proposed, developed, and analyzed. For the first time, the model takes into account the effect of wave-like capillary perturbations of the liquid-gas surface and the acceleration of diffusion in the liquid volume on the absorption rate due to cavitation. According to the results of the model researches, the need for uniform sounding of the extended surface of the liquid film is established to accelerate the absorption of carbon dioxide and other harmful and target gaseous impurities by at least 3 times. The designs and layout of ultrasonic vibration radiators with an extended radiation surface are proposed. The results of measurements of the vibration amplitudes of the invented transducers showed that they have a relative deviation of the amplitude of no more than 0.2. The proposed approaches to the implementation of the process can be recommended for further research, the selection of optimal designs, and industrial applications to accelerate the absorption of gaseous impurities