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
The Volume of Healthy Red Blood Cells is Optimal for Advective Oxygen Transport in Arterioles Wednesday, April 17, 2024 Red blood cells (RBCs) are vital for transporting oxygen from the lungs to the body’s tissues through the intricate circulatory system. They achieve this by binding and releasing oxygen molecules to the abundant hemoglobin within their cytosol. The volume of RBCs affects the amount of oxygen they can carry, yet whether this volume is optimal for transporting oxygen through the circulatory system remains an open question. This study explores, through high-fidelity numerical simulations, the impact of RBC volume on advectve oxygen transport efficiency through arterioles which form the area of greatest flow resistance in the circulatory system. Read more
A structure-based computational model of IP3R1 incorporating Ca and IP3 regulation Monday, April 15, 2024 The inositol 1,4,5-triphosphate receptor (IP3R) mediates Ca release in many cell types and is pivotal to a wide range of cellular processes. High resolution cryo-electron microscopy (Cryo-EM) studies have provided new structural details of IP3R type 1 (IP3R1), showing that channel function is determined by the movement of various domains within and between each of its four subunits. Channel properties are regulated by ligands, such as Ca and IP3, which bind at specific sites and control the interactions between these domains. Read more