Molecular simulations and NMR reveal how lipid fluctuations affect membrane mechanics Saturday, April 27, 2024 (Biophysical Journal 122, 984–1002; March 21, 2023) Read more
A bupropion modulatory site in Gloeobacter violaceus ligand-gated ion channel Friday, April 26, 2024 Bupropion is an atypical antidepressant and smoking cessation drug that causes adverse effects such as insomnia, irritability, and anxiety. Bupropion inhibits dopamine and norepinephrine reuptake transporters and eukaryotic cation-conducting pentameric ligand-gated ion channels (pLGICs), such as nicotinic acetylcholine (nACh) and serotonin type 3A (5-HT3A) receptors, at clinically relevant concentrations. Here, we demonstrate that bupropion also inhibits a prokaryotic homolog of pLGICs, the Gloeobacter violaceus ligand-gated ion channel (GLIC). Read more
Mapping the contribution of C-linker domain to gating polarity in CNBD channels Friday, April 26, 2024 Ion channels of the cyclic nucleotide-binding domain (CNBD) family play a crucial role in the regulation of key biological processes, such as photoreception and pacemaking activity in the heart. These channels exhibit high sequence and structural similarity but differ greatly in their functional responses to membrane potential. The CNBD family includes hyperpolarization-activated ion channels (HCN) and depolarization-activated ether-à-go-go (EAG) channels. Structural and functional studies show that the differences in the coupling interface between these two subfamilies' voltage-sensing domain (VSD) and pore domain may underlie their differential response to membrane polarity. Read more
Exploring the pH dependence of an improved PETase Wednesday, April 24, 2024 Enzymatic recycling of plastic and especially of polyethylene terephthalate (PET) has shown great potential to reduce its negative impact on our society. PET hydrolases (PETases) have been optimized using rational design and machine learning, but the mechanistic details of the PET depolymerization process remain unclear. Belonging to the carboxylic-ester hydrolase family with a canonical Ser-His-Asp catalytic triad, their observed alkaline pH optimum is generally thought to be related to the protonation state of the catalytic His. Read more
Directional change during active diffusion of viral ribonucleoprotein particles through cytoplasm Wednesday, April 24, 2024 A mesh of cytoskeletal fibers, consisting of microtubules, intermediate filaments, and fibrous actin, prevents the Brownian diffusion of particles with a diameter larger than 0.10μm, such as vesicular stomatitis virus ribonucleoprotein particles (RNP), in mammalian cells. Nevertheless, RNP particles do move in random directions, but at a lower rate than Brownian diffusion, which is thermally driven. This nonthermal biological transport process is called active diffusion because it is driven by ATP. Read more
New Insights into the Substrate Recognition and Transport Mechanism of the Human Sodium–Taurocholate Cotransporter Wednesday, April 24, 2024 Read more
Sensing a moving target: a new model reveals how cells sense dynamic signals Wednesday, April 24, 2024 Read more
The Biophysical Function of Pulmonary Surfactant Wednesday, April 24, 2024 The type II pneumocytes of the lungs secrete a mixture of lipids and proteins that together acts as a surfactant. The material forms a thin film on the surface of the liquid layer that lines the alveolar air-sacks. When compressed by the decreasing alveolar surface area during exhalation, the films reduce surface tension to exceptionally low levels. Pulmonary surfactant is essential for preserving the integrity of the barrier between alveolar air and capillary blood during normal breathing. This manuscript focuses on the major biophysical processes by which endogenous pulmonary surfactant achieves its function, and the mechanisms involved in those processes. Read more
Epigenetic marks uniquely tune the material properties of HP1α condensates. Wednesday, April 24, 2024 Biomolecular condensates have emerged as a powerful new paradigm in cell biology with broad implications to human health and disease, particularly in the nucleus where phase separation is thought to underly elements of chromatin organization and regulation. Specifically, it has been recently reported that phase separation of heterochromatin protein 1alpha (HP1α) with DNA contributes to the formation of condensed chromatin states. HP1α localization to heterochromatic regions is mediated by its binding to specific repressive marks on the tail of histone H3, such as trimethylated lysine 9 on histone H3 (H3K9me3). Read more
Photo trapping voltage-gated cardiac sodium channels: inferring local motions at the ‘inactivation gate’ Wednesday, April 24, 2024 Rapid and effectual inactivation in voltage-gated sodium channels is required for canonical action-potential firing. This “fast” inactivation arises from swift and reversible protein conformational changes that utilize transmembrane segments and the cytoplasmic linker between channel domains III and IV. Until recently, fast inactivation had been accepted to rely on a “ball and chain” mechanism whereby a hydrophobic triplet of DIII-IV amino acids (IFM) impairs conductance by binding to a site in central pore of the channel made available by channel opening. Read more
Kinetic cooperativity resolves bidirectional clogging within the nuclear pore complex Thursday, April 18, 2024 As the main gatekeeper of the nucleocytoplasmic transport in eukaryotic cells, the nuclear pore complex (NPC) faces the daunting task of facilitating the bidirectional transport of a high volume of macromolecular cargoes while ensuring the selectivity, speed, and efficiency of this process. The competition between opposing nuclear import and export fluxes passing through the same channel is expected to pose a major challenge to transport efficiency. It has been suggested that phase separation-like radial segregation of import and export fluxes within the assembly of intrinsically disordered proteins that line the NPC pore could be a mechanism for ensuring efficient bidirectional transport. Read more
Transmembrane Determinants of Voltage Gating Differences Between BK (Slo1) and Slo3 Channels Wednesday, April 17, 2024 Voltage-gated potassium channels are critical in modulating cellular excitability, with Slo (slowpoke) channels forming a unique family characterized by their large conductance and dual regulation by electrical signals and intracellular messengers. Despite their structural and evolutionary similarities, Slo1 and Slo3 channels exhibit significant differences in their voltage-gating properties. This study investigates the molecular determinants that differentiate the voltage-gating properties of human Slo1 and mouse Slo3 channels. Read more