Articles Online Now

To provide insight into the basic properties of emerging structures when bacteria or other microorganisms conquer surfaces, it is crucial to analyze their growth behavior during the formation of thin films. In this regard, many theoretical studies focus on the behavior of elongating straight objects. They repel each other through volume exclusion and divide into two halves when reaching a certain threshold length. However, in reality, hardly any object of a certain elongation is perfectly straight.

Biomolecular condensates formed via liquid-liquid phase separation are ubiquitous in cells, especially in the nucleus. While condensates containing one or two kinds of biomolecules have been relatively well characterized, those with more heterogenous biomolecular components and interactions between biomolecules inside are largely unknown. This study used residue-resolution molecular dynamics (MD) simulations to investigate heterogeneous protein assemblies that include four master transcription factors in mammalian embryonic stem cells: Oct4, Sox2, Klf4, and Nanog.

(Biophysical Journal 123, 3452–3462; October 1, 2024)

Significance: MERCs are in focus as they are perceived as Ca2+ signaling hotspots for the rapid transport of ions between the ER and mitochondria. The highly dynamic contact site between the two organelles is anchored by mitofusin 2, and this association changes on demand for Ca2+. Apart from Ca2+ other ion channels in MERCs have not yet been characterized. For the first time, we have shown that Cl- channels are active in MERCs. Cl- ions are implicated in volume regulation, ionic homeostasis, and the fine-tuning of pH. The presence of Cl- currents in MERCs reiterates the physiological significance of Cl- channels in organellar and cellular physiology.

Transposons, DNA sequences capable of relocating within the genome, make up a significant portion of eukaryotic genomes and are often found in clusters. Within the cell nucleus, the genome is organized into chromatin, a structure with varying degrees of compaction due to three-dimensional folding. Transposon insertion or activation can lead to chromatin decompaction, increasing accessibility and potentially facilitating further nearby insertions. This positive feedback between chromatin unfolding and transposon insertion may result in transposon clustering.

Glycolysis is a conserved metabolic pathway that produces ATP and biosynthetic precursors. It is not well understood how the control of mammalian glycolytic enzymes through allosteric feedback and mass action accomplishes various tasks of ATP homeostasis, such as controlling the rate of ATP production, maintaining high and stable ATP levels, ensuring that ATP hydrolysis generates a net excess of energy, and maintaining glycolytic intermediate concentrations within physiological levels. To investigate these questions, we developed a biophysical model of glycolysis based on enzyme rate equations derived from in vitro kinetic data.

Bacteriorhodopsin (bR) is perhaps the best-studied proton pump. Over about four decades, research on this fascinating photocyclic light-driven protein inspired the development of key experimental and computational methodologies that are now widely used in membrane protein studies. We review here failures and successes in computational approaches that have been applied to study the bR proton-transfer steps. Conflict between experimental results pertaining to the proton transfer mechanisms in the early photocycle intermediates was resolved by detailed quantum mechanical/molecular mechanical (QM/MM) computation, the results of which were confirmed more than a decade later.

Amphipathic helices (AHs) are secondary structures that can facilitate binding of proteins to the membrane by folding into a helix with hydrophobic and hydrophilic faces that interact with the same surfaces in the lipid membrane. Septins are cytoskeletal proteins that preferentially bind to domains of micron-scale curvature on the cell membrane. Studies have shown that AH domains in septin are essential for curvature sensing. We present the first computational study of septin AH interactions with lipid bilayers.

Lasso peptides are a unique class of natural products with distinctively threaded structures, conferring exceptional stability against thermal and proteolytic degradation. Despite their promising biotechnological and pharmaceutical applications, reported attempts to prepare them by chemical synthesis result in forming the nonthreaded branched-cyclic isomer, rather than the desired lassoed structure. This is likely due to the entropic challenge of folding a short, threaded motif prior to chemically mediated cyclization.

The pro-apoptotic factor BAX is a key member of the Bcl-2 family of apoptotic regulators. BAX functions by permeating the outer mitochondrial membrane, a process that begins with the targeting of soluble BAX to the membrane. Once associated, BAX refolds, inserts into the bilayer, and ultimately assembles into a multimeric pore of unknown structure. BAX targeting is initiated by an activation signal that can arise from two pathways: (a) a BH3-dependent one in which BAX is activated by one of the BH3-only effectors such as tBid, or (b) a recently discovered BH3-independent pathway, where BAX activity is modulated by changes in lipid composition.

Understanding the structure and dynamics of biological systems is often limited by the trade-off between spatial and temporal resolution. Imaging fluorescence correlation spectroscopy (ImFCS) is a powerful technique for capturing molecular dynamics with high temporal precision but remains diffraction-limited. This constraint poses challenges for quantifying dynamics of subcellular structures like membrane-proximal cortical actin fibers. Computational super-resolution microscopy (CSRM) presents an accessible strategy for enhancing spatial resolution without specialized instrumentation, enabling compatibility with ImFCS.

Chromosome organization mediated by structural maintenance of chromosome complexes is crucial in many organisms. Cohesin extrudes chromatin into loops that are thought to lengthen until it is obstructed by CTCF proteins. In complex cellular environments, the loop extrusion machinery may encounter other chromatin-binding proteins. How these proteins interfere with the cohesin-meditated extrusion process is largely unexplored, but recent experiments have shown that some proteins serve as physical barriers that block cohesin translocation.