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The SLC17 family contains diverse organic anion transporters with various stoichiometries and ion coupling mechanisms. A bacterial protein of this family, the D-galactonate transporter DgoT, co-transports two protons per substrate molecule. While the overall transport cycle of DgoT has been proposed, the role of substrate protonation during its release remains unclear. Galactonate is expected to bind in a deprotonated form due to its low pKa; however, it can be released from the transporter in either a protonated or deprotonated state.

Allosteric effect correlates amino acid residues with entropy transfer with and within proteins in protein complex. Solvation effect could play roles in shaping the allosteric effects. Here we investigate multiple levels of global allosteric correlations within and among proteins in a quaternary antibody-toxin complex, including perturbations of water molecules within first and second solvation shells during all atom MD simulations. Staphylococcal enterotoxin B (SEB) is a potent exotoxin. While monoclonal antibodies 6D3 and 14G8 bind SEB, neither confers significant protection individually, as their epitopes are distal to the TCR/MHC-II interface.

The bacterial flagellar motor (BFM) drives cell motility by rotating the flagellar filament and converting ion flux into mechanical work. At low counter-clockwise (CCW) rotational speeds, the motor operates near the thermodynamic–reversible limit, where torque remains nearly constant against rotation speed for an extended range. With thermodynamic–reversibility previous model study predicts similar behavior in the clockwise (CW) directions independent of the details of torque generation. Structural studies further support this symmetry by showing that the torque-generation machinery in the two directions is essentially mirror-reversed.

Natural fluctuations in gene expression (“noise”) impact many cell processes such as differentiation, proliferation, and apoptosis. Negative feedback gene circuits, a gene self-repressing its own transcription e.g. through protein binding, are often used to reduce the single-gene expression noise and control its impact on investigated phenomena. However, the detailed, quantitative understanding of how temporal and population-level noise is affected by natural mammalian gene expression processes and how this dependence is modified by transcriptional negative feedback is lacking.

Gene regulation emerges from the interplay between chromatin architecture and the molecular interactions that connect enhancers to promoters. To study how these interactions shape transcriptional dynamics, we developed a kinetic model that incorporates multivalent enhancer–promoter binding, transcription factor competition, steric constraints, and chromatin accessibility. The model shows that competition among regulatory factors can generate bistable promoter states at the expense of increased transcriptional noise, revealing a direct relationship between bistability and noise levels.

Microbial rhodopsins represent a diverse superfamily of light-sensitive proteins composed of seven transmembrane helices with expanding phylogenetic diversity driven by advances in metagenomics. Among these, schizorhodopsins constitute a divergent family originally identified as inward proton pumps from Promethearchaeota (Asgard archaea). Here, we report that in addition to archaeal schizorhodopsins, many members of the family originate from bacteria and detail a comprehensive biophysical characterization of two schizorhodopsins from uncultured Antarctic bacteria: paSzR from Minisyncoccota (Patescibacteria) and psSzR from a Pseudanabaenacea cyanobacterium.

One of the crucial processes in the lifespan of the eukaryotes is membrane fusion, which mediates various important cellular events. The process is utilized by enveloped viruses to enter the host cells and cause viral infection. The study of the stability of fusion intermediates and the kinetics of evolution of states becomes crucial to understand the membrane fusion mechanism in detail. In this work, we have studied the temperature-dependent fusion in the absence and presence of two coronin 1-derived WD repeat-containing inhibitory peptides, AG-22 and mTG-23, to unravel the inhibitory mechanism of these peptides.

Cryo-electron microscopy (cryoEM) is a powerful tool for atomic- and molecular-resolution structure determination, while molecular dynamics (MD) simulations are similarly powerful tools for predicting molecular trajectories. Given the challenges in estimating biomolecule dynamics with cryoEM alone, MD simulations are employed to forecast molecular motions and to interpret cryoEM reconstructions. Few methods, however, can evaluate MD predictions directly. Here, we use multislice wave propagation to project sampled snapshots of MD trajectories, either coarse-grained (CG) or all-atom (AA), into simulated cryoEM 3D reconstructions.

Protein-DNA co-condensates where protein and DNA condensates co-localize, formed through liquid-liquid phase separation, play critical roles in gene expression, cancer and developmental defects. Recent experimental studies have revealed the impact of mechanical stress on these co-condensates, but their dynamic processes and microscopic structures remain poorly characterized. Using coarse-grained molecular dynamics simulations, we investigated the nanoscale natures of FUS and DNA co-condensation under DNA stretching.

The protein vinculin mediates actin-myosin-dependent adhesion strength to regulate force transmission at cellular adhesions. The precise distribution of forces sensed by vinculin that regulates downstream cellular processes remains unclear. To determine vinculin tension in multiple cell types, a FRET-based tension-sensitive module was knocked into the vinculin locus of human induced pluripotent stem cells. Measurements of vinculin tension and adhesion spatial distributions were used to create mechanical profiles that identify cellular origin and differentially correlate to cell shape characteristics.