Knowledge of RNA 3-dimensional (3D) structures is critical to understanding the important biological functions of RNAs. Although various structure prediction models have been developed, the high-accuracy predictions of RNA 3D structures are still limited to the RNAs with short lengths or with simple topology. In this work, we proposed a new model, namely FebRNA, for building RNA 3D structures through

Transmembrane protein 16F (TMEM16F) is a ubiquitously expressed Ca2+-activated phospholipid scramblase that also functions as a largely non-selective ion channel. Though recent structural studies have revealed the closed and intermediate conformations of mammalian TMEM16F (mTMEM16F), the open and conductive state remains elusive. Instead, it has been proposed that an open hydrophilic pathway may not

Rigidity of extracellular matrix markedly regulates many cellular processes. However, how cells detect and respond to matrix rigidity remains incompletely understood. Here, we propose a unified two-dimensional multiscale framework accounting for the chemomechanical feedback to explore the interrelated cellular mechanosensing, polarization, and migration, which constitute the dynamic cascade in cellular

Selective gene regulation is mediated by recognition of specific DNA sequences by transcription factors (TF). The extremely challenging task of searcnthing out specific cognate DNA binding sites among several million putative sites within the eukaryotic genome is achieved by complex molecular recognition mechanisms. Elements of this recognition code include the core binding sequence, the flanking sequence

Polymyxins are increasingly used as the last-line therapeutic option for the treatment of infections caused by multidrug-resistant Gram-negative bacteria. However, efforts to address the resistance in superbugs are compromised by a poor understanding of the bactericidal modes because high-resolution detection of the cell structure is still lacking. By performing molecular dynamics simulations at a

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An approach for the efficient simulation of phase-separated lipid bilayers, for use in the calculation of equilibrium free energies of partitioning between lipid domains, is proposed. The methodology exploits restraint potentials and rectangular aspect ratios that enforce lipid phase separation, allowing for the simulation of smaller systems that approximately reproduce bulk behavior. The utility of

It has been demonstrated experimentally that slow and fast conduction waves with distinct conduction velocities can occur in the same nerve system depending on the strength or the form of the stimulus, which give rise to two modes of nerve functions. However, the mechanisms remain to be elucidated. In this study, we use computer simulations of the cable equation with modified Hodgkin-Huxley kinetics

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Site-directed spin labeling (SDSL) electron paramagnetic resonance (EPR) spectroscopy is a powerful technique for the investigation of protein structure and dynamics. Accurate spin label modeling methods are essential to make full quantitative use of SDSL EPR data for protein modeling and model validation. Using a set of DEER data from seven different site pairs on maltodextrin/maltose-binding protein

Thrombosis, resulting in occlusive blood clots, blocks blood flow to downstream organs and causes life threatening conditions such as heart attacks and strokes. The administration of tissue plasminogen activator (t-PA) that drives the enzymatic degradation (fibrinolysis) of these blood clots is a treatment for thrombotic conditions, but the use of these therapeutics is often limited due to the time

Engineered signaling proteins permit precise modulation of cell signaling networks and are valuable tools for basic and translational research. In this issue of Structure, Tichy and colleagues leverage high-resolution GPCR-G protein complex structures to rationally design improved light-activated chimeric GPCRs (termed OptoXRs) with increased sensitivity and tunable signaling features.

In this issue of Structure, van der Kant and colleagues use a computational approach to uncover what dictates assembly of proteins into amyloid fibrils. Structurally distinct amyloids have about 30% of their residues predisposed to cross-β conformation, while less favorable regions may be the source of polymorphism by interacting with stabilizing cofactors.

Accurate protein structure predictors use clusters of homologues, which disregard sequence specific effects. In this issue of Structure, Weißenow and colleagues report a deep learning-based tool, EMBER2, that efficiently predicts the distances in a protein structure from its amino acid sequence only. This approach should enable the analysis of mutation effects.

The transient disruption of membranes for the passive permeation of ions or small molecules is a complex process relevant to understanding physiological processes and biotechnology applications. Phenolic compounds are widely studied for their antioxidant and antimicrobial properties, and many biological activities of phenolic compounds are based on their interactions with membranes. Ions are ubiquitous

We investigate the effects on the distribution of lipids in the plasma membrane that are caused by the insertion of a protein, Piezo1, that significantly distorts the membrane toward the cytosol. From coarse-grained molecular dynamics simulations, we find that the major effects occur in the outer, extracellular, leaflet. The mol fraction of cholesterol increases significantly in the curved region of

BamA, the core component of the β-barrel assembly machinery (BAM) complex, is an integral outer membrane protein (OMP) in Gram-negative bacteria that catalyzes the folding and insertion of OMPs. A key feature of BamA relevant to its function is a lateral gate between its first and last β-strands. Opening of this lateral gate is one of the first steps in the asymmetric-hybrid-barrel model of BamA function

Macrophages use filopodia to withdraw particles towards the cell body for phagocytosis. This can require substantial forces, which the cell generates after bio-mechanical stimuli are transmitted to the filopodium. Adaptation mechanisms to mechanical stimuli are essential for cells, but can a cell iteratively improve filopodia pulling? If so, the underlying mechanic adaptation principles organized on

Membrane reshaping is an essential biological process. The chemical composition of lipid membranes determines their mechanical properties, and thus the energetics of their shape. Hundreds of distinct lipid species make up native bilayers, and this diversity complicates efforts to uncover what compositional factors drive membrane stability in cells. Simplifying assumptions, therefore, are used to generate

Many lipid membranes of eukaryotic cells are asymmetric, which means the two leaflets differ in at least one physical property, such as lipid composition or lateral stress. Maintaining this asymmetry is helped by the fact that ordinary phospholipids rarely transition between leaflets, but cholesterol is an exception: its flip-flop times are in the microsecond range, so that its distribution between

Actin networks rely on nucleation mechanisms to generate new filaments because spontaneous nucleation is kinetically disfavored. Branching nucleation of actin filaments by Actin related protein (Arp2/3), in particular, is critical for actin self-organization. In this study, we use the simulation platform for active matter, MEDYAN, to generate 2000s long stochastic trajectories of actin networks, under

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Single-molecule counting techniques enable a precise determination of the intracellular abundance and stoichiometry of proteins and macromolecular complexes. These details are often challenging to quantitatively assess yet are essential for our understanding of cellular function. Consider G protein-coupled receptors (GPCRs)—an expansive class of transmembrane signalling proteins that participate in

Cyclic lipopeptides (CLiPs) have many biological functions, including the selective permeabilization of target membranes, and technical and medical applications. We studied the anionic CLiP viscosin from Pseudomonas along with a neutral analog, pseudodesmin A, and the cationic viscosin-E2K to better understand electrostatic effects on target selectivity. Calcein leakage from liposomes of anionic phosphatidylglycerol

Development of a robust, uniform, and magnetically orientable lipid mimetics will undoubtedly advance solid-state NMR of macroscopically aligned membrane proteins. Here we report on a novel lipid membrane mimetic based on peptoid belts. The peptoids composed of 15 residues were synthesized by alternating N-(2-carboxyethyl)glycine with N-(2-phenethyl)glycine residues at the 2:1 molar ratio. The chemically

Zika virus (ZIKV) is a positive-sense single-stranded RNA virus that infects humans and can cause birth defects and neurological disorders. Its non-structural protein 3 (NS3) contains a protease domain and a helicase domain, both of which play essential roles during the viral life cycle. However, it has been shown that ZIKV NS3 has an inherently weak helicase activity, making it unable to unwind long

This manuscript studies the impact of extruding hairpins on two-dimensional self-assembly of DNA tiles on solid surface. Hairpins are commonly used as tomographic markers in DNA nanostructures for atomic force microscopy (AFM) imaging. In this study, we have discovered that hairpins play a more active role. They modulate the adsorption of the DNA tiles onto the solid surface, thus, change the tile

As the bacterial multidrug resistance crisis continues, membrane-active antimicrobial peptides (AMPs) have emerged as an alternate treatment to conventional antibiotics. In contrast to these AMPs, which largely function by a non-specific membrane disruption mechanism, we describe a series of transmembrane (TM) peptides that are designed to act as drug efflux inhibitors by aligning with and out-competing

For heart failure (HF) patients, myocardial ATP level can be reduced to one half of that observed in healthy controls. This marked reduction (from ≈ 8 mM in healthy controls to as low as 3-4 mM in HF) has been suggested to contribute to impaired myocardial contraction, and to the decreased pump function characteristic of heart failure. However, in vitro measures of maximum myofilament force generation