BJ Articles Ahead of Print

The cell surface receptor Neuropilin-1 (Nrp1) was recently identified as a host factor for SARS-CoV-2 entry. Spike protein of SARS-CoV-2 is cleaved into two segments, the S1 (res. 1-685) and the S2 (res. 686-1273) domain by furin protease. Nrp1 predominantly binds to the C-terminal RRAR motif (res. 682-685) of the S1 domain. In this study, we firstly modeled the association of a Nrp1 protein (consisting of domains a2-b1-b2) with the Spike protein. Next, we studied the separation of S2 from the S1 domain, with and without Nrp1 bound, by utilizing molecular dynamics pulling simulations.

Clinical syndrome coronavirus disease 2019 (COVID-19) induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by rapid spreading and high mortality worldwide. While the pathology is not yet fully understood, hyper-inflammatory response and coagulation disorders leading to congestions of microvessels are considered to be key drivers of the still increasing death toll. Until now, physical changes of blood cells have not been considered to play a role in COVID-19 related vascular occlusion and organ damage.

Protein aggregation is involved in a variety of diseases, including neurodegenerative diseases and cancer. The cellular environment is crowded by a plethora of cosolutes comprising small molecules and biomacromolecules at high concentrations, which may influence the aggregation of proteins in vivo. To account for the effect of cosolutes on cancer-related protein aggregation, we studied their effect on the aggregation of the cancer-related L106R mutant of the Axin protein. Axin is a key player in the Wnt signaling pathway, and the L106R mutation in its RGS domain results in a native molten globule that tends to form native-like aggregates.

Many species show a diverse range of sizes; for example, domestic dogs have large variation in body mass. Yet, the internal structure of the organism remains similar, i.e. the system scales to organism size. Drosophila melanogaster has been a powerful model system for exploring scaling mechanisms. In the early embryo, gene expression boundaries scale very precisely to embryo length. Later in development, the adult wings grow with remarkable symmetry and scale well with animal size. Yet, our knowledge of whether internal organs initially scale to embryo size remains largely unknown.

Large-scale conformational transitions in the spike protein S2 domain are required during host cell infection of the SARS-CoV-2 virus. Although conventional molecular dynamics simulations have been extensively used to study therapeutic targets of SARS-CoV-2, it is still challenging to gain molecular insight into the key conformational changes due to the size of the spike protein and the long timescale required to capture these transitions. In this work, we have developed an efficient simulation protocol that leverages many short simulations, a novel selection algorithm, and Markov state models to interrogate the dynamics of the S2 domain.

Muscle stem cells (MuSCs) are requisite for skeletal muscle regeneration and homeostasis. Proper functioning of MuSCs, including activation, proliferation, and fate decision, is determined by an orchestrated series of events and communication between MuSCs and their niche. A multitude of biochemical stimuli are known to regulate MuSCs fate and function. However, in addition to biochemical factors, it is conceivable that MuSCs are subjected to mechanical forces during muscle stretch-shortening cycles due to myofascial connections between MuSCs and myofibers.

— The question of how much information the photoplethysmogram (PPG) signal contains on the autonomic regulation of blood pressure (BP) remains unsolved. This study aims to compare the low-frequency (LF) and high-frequency (HF) components of PPG and BP and assess their correlation with oscillations in interbeat intervals (RR intervals) at similar frequencies.

The folding stability of a protein is governed by the free-energy difference between its folded and unfolded states, which results from a delicate balance of much larger but almost compensating enthalpic and entropic contributions. The balance can therefore easily be shifted by an external disturbance, such as a mutation of a single amino acid or a change of temperature, in which case the protein unfolds. Effects like cold denaturation, in which a protein unfolds due to cooling, provide evidence that proteins are strongly stabilized by the solvent entropy contribution to the free energy balance.

Spin labels based on cinobufagin, a specific inhibitor of the Na,K-ATPase, have proved valuable tools to characterize the binding site of cardiotonic steroids (CTS), which also constitutes the extracellular cation pathway. Because existing literature suggests variations in the physiological responses caused by binding of different CTS, we extended the original set of spin-labelled inhibitors to the more potent bufalin derivatives. Positioning of the spin labels within the Na,K-ATPase site was defined and visualized by molecular docking.

Within the nucleus of the eukaryotic cell, DNA is partitioned into domains of highly condensed transcriptionally silent heterochromatin and less condensed transcriptionally active euchromatin. Heterochromatin protein 1α (HP1α) is an architectural protein that establishes and maintains heterochromatin, ensuring genome fidelity and nuclear integrity. While the mechanical effects of changes in the relative amount of euchromatin and heterochromatin brought about by inhibiting chromatin modifying enzymes have been studied previously, here we measure how the material properties of the nuclei are modified following the knockdown HP1α.

The leukocyte specific β2-integrin LFA-1, and its ligand ICAM-1 expressed on endothelial cells (ECs), are involved in the arrest, adhesion and transendothelial migration of leukocytes. Although the role of mechanical forces on LFA-1 activation is well-established, the impact of forces on its major ligand ICAM-1, has received less attention. Using a parallel-plate flow-chamber combined with confocal and super-resolution microscopy, we show that prolonged shear-flow induces global translocation of ICAM-1 on ECs upstream of flow direction.

Proteins of halophilic organisms, which accumulate molar concentrations of KCl in their cytoplasm, have a much higher content in acidic amino acids than proteins of mesophilic organisms. It has been proposed that this excess is necessary to maintain proteins hydrated in an environment with low water activity: either via direct interactions between water and the carboxylate groups of acidic amino acids, or via cooperative interactions between acidic amino acids and hydrated cations. Our simulation study of 5 halophilic proteins and 5 mesophilic counterparts does not support either possibility.