Humans and other animals wittingly or unwittingly run risk–benefit analyses daily. For animals of reproductive age, a prime example of such analysis is assessing the benefit of reproductive success versus the cost of being preyed upon. The scale needs to be sensitive: over-prioritize survival at the risk of a lack of progeny, or undermine danger at the risk of perishing. While previous studies and

Despite their large functional diversity and poor sequence similarity, tetrameric and pseudo-tetrameric potassium, sodium, calcium and cyclic-nucleotide gated channels, as well as two-pore channels, transient receptor potential channels and ionotropic glutamate receptors share a common folding pattern of the transmembrane (TM) helices in the pore-forming domain. In each subunit or repeat, the pore

Breast tumors are typically surrounded by extracellular matrix (ECM) that is heterogeneous, not just structurally but also mechanically. Conventional rheometry is inadequate for describing cell-size-level spatial differences in ECM mechanics that are evident at micrometer scales. Optical tweezers and passive microrheometry provide a microscale resolution for the purpose but are incapable of measuring

G-Protein coupled receptors (GPCRs) represent one of the largest classes of therapeutic targets. However, developing successful therapeutics to target GPCRs is a challenging endeavor with many molecules failing during in vivo clinical trials due to a lack of efficacy. The in vitro identification of drug targeted residence time (1/koff) has been suggested to improve prediction of in vivo success. Here

As 2024 closes, we take this opportunity to reflect on the highlights of our 30th anniversary year and consider what the future holds for the field.

In eukaryotic cells, the phospholipid cardiolipin (CL) is a crucial component that influences the function and organization of the mitochondrial inner membrane. In this study, we examined its potential role in passive proton transmembrane flux using unilamellar vesicles composed of natural egg phosphatidylcholine (PC) alone or with the inclusion of 18 or 34 mol% CL. A membrane potential was induced

NOTCH, a single-pass transmembrane protein, plays a crucial role in cell fate determination through cell-to-cell communication. It interacts with two canonical ligands, Delta-like (DLL) and Jagged (JAG), located on neighboring cells to regulate diverse cellular processes. Despite extensive studies on the functional roles of NOTCH and its ligands in cellular growth, the structural details of full-length

Cyanobacteria are responsible for up to 80% of aquatic carbon dioxide fixation and have evolved specialized carbon concentrating mechanism to increase photosynthetic yield. As such, cyanobacteria are attractive targets for synthetic biology and engineering approaches to address the demands of global energy security, food production, and climate change for an increasing world's population. The bicarbonate

Physical spatiotemporal characteristics of cellular cortex dominate cell functions and even determine cell fate. The cellular cortex is able to re-organize to a dynamic steady status with changed stiffnesses once stimulated, and thus alter the physiological and pathological activities of almost all types of cells. TGF-β2, a potent pleiotropic growth factor, plays important roles in cartilage development

In this issue of Structure, Nguyen et al.1 reveal that amyloid fibrils of the transthyretin (TTR) V30M variant from the heart and nerves of the same patient exhibit structural homogeneity. This finding is crucial for advancing our understanding of V30M-TTR amyloid deposition, which leads to fatal ATTRv amyloidosis.

In this issue of Structure, Viennet et al.1 report a study characterizing the DNA binding by a three-zinc-finger fragment from the transcription factor BCL11A, with the unusual feature that an interfinger interaction in the free protein is disrupted during binding, which provides a positive entropic contribution that enhances the affinity.

In this issue of Structure, Kielkopf et al.1 report the crystal structures of Rhs proteins that are genetically fused to the type VI secretion system …

Experimentally monitoring the kinematics of branching network growth is a tricky task, given the complexity of the structures generated in three dimensions. One option is to drive the network in such a way as to obtain two-dimensional growth, enabling a collection of independent images to be obtained. The density of the network generates ambiguous structures, such as overlaps and meetings, which hinder

Stomatocyte-discocyte-echinocyte (SDE) transformations in human red blood cells (RBCs) have significant influences on blood dynamics and related disorders. The mechanical properties of the RBC membrane, such as shear modulus and bending elasticity, play crucial roles in determining RBC shapes. Recent biophysical findings reveal that building a comprehensive model capable of describing SDE shape transformations

A comment on how easy (or difficult) it is to find a stucture of interest and some suggestions on what could be done to start to address the problem.

The cochlea’s mechanical response to sound stimulation is nonlinear, likely due to saturation of the mechanoelectric transduction current that is part of an electromechanical feedback loop. The ability of a second tone or tones to reduce the response to a probe tone is one manifestation of nonlinearity, termed suppression. Using optical coherence tomography to measure motion within the organ of Corti

We review empirical methods that can be used to provide physical descriptions of dynamic cellular processes during development and disease. Our focus will be nonspatial descriptions and the inference of underlying interaction networks including cell-state lineages, gene regulatory networks, and molecular interactions in living cells. Our overarching questions are: How much can we learn from just observing

Chromaffin cells of the adrenal medulla have an important role in the sympathetic stress response. They secrete catecholamines and other hormones into the bloodstream upon stimulation by the neurotransmitter pituitary adenylate cyclase-activating polypeptide (PACAP). PACAP causes a long-lasting and robust secretory response from chromaffin cells. However, the cellular mechanisms by which PACAP causes

Metals are essential components for the structure and function of many proteins. However, accurate modelling of their coordination environments remains a challenge due to the complexity and diversity of metal-coordination geometries. To address this, a method is presented for extracting and analysing coordination information, including bond lengths and angles, from the Crystallography Open Database

Recently, the conclusions drawn from crystallographic data about the number of oxygen ligands associated with the CaMn4 cofactor in the oxygen-evolving center (OEC) of Thermosynechococcus vulcanus photosystem II (PSII) have been called into question. Here, using OEC-omit, metal ion-omit and ligand-omit electron-density maps, it is shown that the number of oxygen ligands ranges from three in the functional

The type IV pilus is a diverse molecular machine capable of conferring a variety of functions and is produced by a wide range of bacterial species. The ability of the pilus to perform host-cell adherence makes it a viable target for the development of vaccines against infection by human pathogens such as Pseudomonas aeruginosa. Here, the 1.3 Å resolution crystal structure of the N-terminally truncated

The structure and dynamics of the cell nucleus regulate nearly every facet of the cell, and changes in nuclear shape can limit cell motility. Although the nucleus is generally seen as the stiffest organelle in the cell, cells can nevertheless deform the nucleus to large strains by small mechanical stresses. Here, we show that the mechanical response of the cell nucleus exhibits active fluidization

Structural biology beats at the heart of modern science. It reveals the molecular mechanisms underlying disease processes, facilitating drug and vaccine development, and improving existing therapies. Beyond healthcare, it has an important role in agriculture, biotechnology, food safety and environmental sustainability. Therefore, structural biology is integral to achieving the United Nations Sustainable

Structural biology has continued to advance over the past decades, owing to the development of improved and new technologies. The launch of Nature Structural Biology (NSB) in 1994 provided a much-needed avenue for the dissemination of these advances. This year marks the thirtieth anniversary of the journal, now named Nature Structural and Molecular Biology. Although it has expanded far beyond the initial

Studying native protein structures at near-atomic resolution in a crowded environment presents challenges. Consequently, understanding the structural intricacies of proteins within pathologically affected tissues often relies on mass spectrometry and proteomic analysis. Here, we utilized cryoelectron microscopy (cryo-EM) and the Build and Retrieve (BaR) method to investigate protein complexes’ structural

Rectification, the tendency of bidirectional ionic conductors to favor ion flow in a specific direction, is an intrinsic property of many ion channels and synthetic nanopores. Despite its frequent occurrence in ion channels and its phenomenological explanation using Eyring’s rate theory, a quantitative relationship between the rectified current and the underlying ion-specific and voltage-dependent

Optical tweezer (OT) single-molecule force spectroscopy is a powerful method to map out the energy landscape of biological complexes and has found increasing applications in academic and pharmaceutical research. The dominant method to extract molecular conformation transitions from the thermal diffusion-broadened trajectories of the microscopic OT probes attached to the single molecule of interest

Fluorine-19 is an ideal nucleus for studying biological systems using NMR due to its rarity in biological environments and its favorable magnetic properties. In this work, we used a mixture of monofluorinated palmitic acids (PAs) as tracers to investigate the molecular interaction of the fluorinated drug rosuvastatin in model lipid membranes. More specifically, PAs labeled at the fourth and eighth

Microtubule stability is known to be governed by a stabilizing GTP/GDP-Pi cap, but the exact relation between growth velocity, GTP hydrolysis, and catastrophes remains unclear. We investigate the dynamics of the stabilizing cap through in vitro reconstitution of microtubule dynamics in contact with microfabricated barriers, using the plus-end binding protein GFP-EB3 as a marker for the nucleotide state

Ca2+ blinks measure the exit of Ca2+ from the junctional sarcoplasmic reticulum (JSR) in a cardiac myocyte during a Ca2+ spark. Here, the relationship between experimental blink fluorescence measurements and the [Ca2+] in the JSR is explored using long 3D simulations of diastolic Ca2+ release. For a fast intra-SR Ca2+-activated fluorophore such as Fluo-5N, we show that a simple mathematical formula

It is interesting to find pathologically that leukocytes, especially neutrophils, tend to adhere in the liver sinusoids dominantly but not in the postsinusoidal venules. While both views of receptor-ligand interactions and physical trapping are proposed for mediating leukocyte adhesion in liver sinusoids, integrated investigations for classifying their respective contributions are poorly presented