Accounting for Missed Events in the Bayesian Modeling of IP3R2 Multimodal Gating Wednesday, October 7, 2026 The Inositol 1,4,5-trisphosphate receptor channel (IP3R) is an important calcium channel involved in calcium-induced calcium release, playing a prominent role in intracellular calcium signaling. However, accurately characterizing its gating behavior remains a challenge, particularly due to the temporal resolution of patch clamp techniques that is not large enough to detect all short-lived events. This limitation can significantly bias the inference of kinetic models describing the receptor activity. Read more
Molecular Mechanism of pH-Dependent Activation in Human Equilibrative Nucleoside Transporter 3 Wednesday, October 7, 2026 Human equilibrative nucleoside transporter 3 (hENT3) is a lysosomal transporter whose activity is strictly dependent on an acidic lumenal environment. Mutations in hENT3 lead to H syndrome and other metabolic disorders, yet the structural basis for its pH-sensitive gating remains poorly defined. Using multi-replica conventional MD simulations, we provide atomistic insight into the pH-dependent activation mechanism of hENT3 in the outward-facing state. Protonated Asp219 triggers a local hydrogen-bond reorganization that recruits conserved Ser229 and the TM6 helix-capping residue Asp225 and stabilizes TM5—an intrinsically flexible helix within the ENT family. Read more
Thermodynamic Drivers of LINC Complex Clustering in the Nuclear Envelope Wednesday, October 7, 2026 The Linker of Nucleus to Cytoskeleton (LINC) complex is a central mechanical element of the nuclear envelope, transmitting cytoskeletal forces to the nucleus and coordinating nuclear mechanics. While individual LINC complex units (LCUs) are well characterized structurally, growing experimental evidence suggests that LCUs assemble into higher-order clusters whose organization may critically influence force transmission. However, the molecular drivers of LINC complex clustering and their stability in the absence of externally applied forces remain poorly understood. Read more
Modeling Protein Diffusion Across ER–Nuclear Envelope Junctions Reveals Efficient Transport via Simple Diffusion Tuesday, October 6, 2026 The endoplasmic reticulum (ER) is the largest continuous membrane-bound organelle in the cell and plays a central role in the synthesis and turnover of lipids and proteins. It connects directly to the nucleus through specialized contact sites known as ER–nuclear envelope (NE) junctions. In a recent study, we showed that these junctions are sparse and highly constricted, measuring less than 20 nm in diameter and occurring at a frequency of approximately 0.1 junctions per square micrometer. However, it remains unclear whether such limited and narrow connections are sufficient to support efficient transport between the ER and NE. Read more
VARIANT: Web Server for Decoding and Analyzing Viral Mutations at Genome and Protein Levels Tuesday, October 6, 2026 A comprehensive analysis of viral mutations is essential for understanding viral evolution, disease epidemiology, diagnosis, drug resistance, and immune escape. However, challenges remain in capturing complex mutation patterns and supporting diverse viral families with varying genome architectures. To address these challenges, we present VARIANT, an openly accessible web server for mutational analysis of RNA viral genomes and associated viral products across both single- and multi-segment virus genomes. Read more
Reflectin Proteins Form Net Charge Density-Tuned Multiphase Condensates That May Facilitate Spatial Organization in Squid Skin Bragg Lamellae Tuesday, October 6, 2026 The reflectins are cationic proteins that transduce neuronal signals tuning skin color for dynamic camouflage and communication in Loliginid squid. Neuronally released acetylcholine (ACh) activates phosphorylation of the reflectins, triggering their condensation, folding and hierarchical assembly. These changes drive proportional osmotic and Gibbs-Donnan dehydration of membrane-enclosed Bragg lamellae containing these proteins in skin cells called iridocytes, resulting in the calibrated, progressive change their refractive index and spacing to finely tune the wavelength of reflected light. Read more
Mechanisms of protein transport between subcompartments of the cone photoreceptor outer segment membrane system Wednesday, September 30, 2026 (≤300 words, current = 296): Retinal cone photoreceptor outer segments (COS) are modified cilia where light is transduced into electrical signals. While extensive ultrastructural studies have established that the COS membrane system consists of several hundred parallel lamellae interconnected by the ciliary plasma membrane (PM) through narrow membrane bridges known as saddle points (SP), little is known about how components of the phototransduction cascade are delivered to COS, how they are loaded into flat lamellae surfaces (LS) and how they maintain uniform distribution among lamellae, especially in light of the steeply tapered lamellar geometry found in some species and high membrane turnover rate. Read more
A Mechanochemical Model for Frequency Entrainment and Bursting Transitions in Cardiac Calcium Oscillations Wednesday, September 30, 2026 Rhythmic contraction of cardiomyocytes is driven by self-sustained intracellular calcium oscillations. While these oscillations are typically attributed to intrinsic calcium cycling, increasing experimental evidence indicates that external mechanical forces can modulate calcium oscillation frequency and lead to frequency entrainment. However, the physical mechanisms underlying such mechanical entrainment remain unclear. Here, we develop a minimal mechanochemical model that couples intracellular calcium cycling, adaptive ryanodine receptor (RyR) gating, and strain-induced reactive oxygen species (ROS) signaling to investigate how external mechanical forces reshape the nonlinear dynamics of autonomous calcium oscillations in cardiomyocytes. Read more
In Vitro Wrapping of Non-Enveloped Viral Capsids with Lipid Bilayers Wednesday, September 30, 2026 In vitro reconstituted virus-like particles (VLPs) – particles with structure identical to those of virus particles except for containing non-infectious genetic information instead of a viral genome – are promising nanocarriers for delivery of therapeutic cargos. Among the simplest examples are the VLPs formed from the capsid protein (CP) of either Cowpea Chlorotic Mottle Virus (CCMV) or Brome Mosaic Virus (BMV), which form spontaneously from purified components upon mixing CCMV or BMV CP with single-stranded RNA under the right pH and ionic strength conditions. Read more
Ground-state chromophore geometry, not cage size, tracks quantum yield in fluorescent proteins Tuesday, September 29, 2026 A common explanation for brightness variation in fluorescent proteins (FPs) is that tight chromophore cages produce bright proteins. This model predicts that quantum yield should track the dihedral rotational space available to the chromophore. We tested that prediction across 838 FP crystal structures from the Protein Data Bank.For each structure, we scanned the chromophore's two methine-bridge torsions, τ and φ. We measured two features of the chromophore environment: the fraction of torsional space that is sterically accessible, and the angular distance from the deposited chromophore to the nearest planar geometry. Read more
A small processivity of kinesin-14 motors can enhance sliding velocity of antiparallel microtubules Tuesday, September 29, 2026 Members of kinesin-14 family motors, which can move toward the microtubule (MT) minus end, play roles in spindle assembly and maintenance during mitosis and meiosis. Some kinesin-14 motors are non-processive while others are processive. Here, we study both theoretically and numerically the dynamics of the MT gliding and relative sliding of antiparallel MTs by multiple kinesin-14 motors. We show that while the published experimental data on the MT gliding and sliding by multiple kinesin-14 HSET motors cannot be explained by considering that the HSET is non-processive, they are well explained by a model in which HSET has a small processivity. Read more