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Photosynthetic microorganisms rely on multiple central-carbon-metabolism pathways to adapt to fluctuating light and energy availability across diel cycles. Mechanistic insight into the regulatory dynamics of this adaptation requires integrating processes that operate across disparate timescales, from rapid redox-dependent post-translational modifications (PTMs) to slower changes in protein expression and metabolic pathway usage. Here, we develop a whole-cell four-dimensional (3D + time) model of the marine cyanobacterium Prochlorococcus marinus MED4 that explicitly represents the spatial, subcellular organization of key carbon fixation enzymes and genetic information processes coupled to a non-spatial genome-scale metabolic model (GSMM).

Multidomain proteins connected by flexible linkers populate conformational ensembles that are challenging to characterize using conventional structural biology methods. In domain–linker–domain (DLD) proteins, linker-mediated inter-domain relative positions and orientations are functionally relevant, yet their dynamical behavior in solution normally remain poorly described. Small-angle X-ray scattering (SAXS) provides ensemble-averaged structural information for such systems; however, coupling with computational modeling is required to accurately describe the dynamic behavior of this family of proteins in solution.

Although traditional molecular dynamics simulations successfully capture a variety of different molecular interactions, the protonation states of titratable residues are kept static. A recent constant-pH molecular dynamics implementation in the GROMACS package allows pH effects to be captured dynamically, and promises to provide both the accuracy and computational performance required for studying pH-mediated conformational dynamics in large, complex systems containing hundreds of titratable residues.

The homotrimeric SARS-CoV-2 spike glycoprotein comprises two subunits: S1, which recognizes host-receptors through its receptor-binding domains (RBDs), and S2, anchored to the viral membrane through its transmembrane domain (TMD), which facilitates the fusion of the viral envelope with the host cell membrane. Upon host-receptor engagement and proteolytic activation, S1 dissociates and triggers a large conformational transition in S2, involving structural rearrangements in the S2 ectomembrane-domains and the TMD.

Integrins are bidirectional mechanochemical receptors that transmit signals upon ligand binding to the cytoskeleton (outside-in) and cytoskeletal forces back across the membrane (inside-out) to the integrin-ligand bond. Integrins are activated prior to ligand binding, which involves large conformational rearrangements across the extracellular, transmembrane, and cytoplasmic regions. While the conformational and energetic basis of outside-in activation is increasingly well defined, the mechanical forces required for separating the tightly packed αβ transmembrane (TM) helices during inside-out signaling remain largely unknown.

Several members of the adhesion subfamily of G protein-coupled receptors (aGPCRs) are capable of self-activation by an internal agonist sequence (aka the Stachel) that’s exposed upon removal or conformational changes of the N-terminal fragment of the receptor. Synthetic peptides derived from the Stachel sequence can be used as exogenous agonists. In the inactive form of the full-length receptor, the Stachel is sequestered as the β13-strand within the GPCR Autoproteolysis-INducing (GAIN) domain, but it engages the seven transmembrane region as a helix when it is either an intramolecular sequence or a synthetic peptide.

Macromolecular crystallography has historically inferred models of internal crystal architecture from reciprocal-space measurements of Bragg reflections. Nevertheless, direct real-space visualization of crystallographic disorder remains elusive, particularly at the nanoscale. Using a 15-nanometer probe, here we apply both ambient-temperature and cryogenic four-dimensional scanning transmission electron microscopy (4D–STEM) to map the topography of coherently diffracting domains (CDDs) in lysozyme and myoglobin microcrystals at length scales 100 × finer than conventional X-ray and electron beams.

Within the islets of Langerhans, pancreatic beta cells coordinate pulsatile insulin release that is essential for metabolic homeostasis. This coordination emerges from complex intercellular coupling and unfolds at least on three nested timescales: (i) slow, metabolism-driven oscillations lasting several minutes; (ii) fast, electrically driven bursts of a few seconds; and (iii) ultrafast action-potential spikes on the order of tens of milliseconds. To unravel the principles governing this multiscale collective behavior and its link to secretion, we developed a phenomenological multicellular mathematical model based on realistic intercellular interaction patterns and combined it with timescale-specific functional connectivity analysis.

Cancer cells in hypoxic environments often proliferate less but exhibit enhanced migration relative to their normoxic counterparts. Recent in vitro and in silico studies have characterized the role of hypoxic memory – the ability of cancer cells to retain their hypoxic phenotype even when reoxygenated – in tumor invasion. However, the observations have been limited either to exposing cancer cells to hypoxia for a fixed duration or by assuming a fixed-time persistence of the hypoxic state upon reoxygenation independent of the duration of hypoxia exposure.

The ion channel TRPV1 is expressed in the peripheral nervous system where it mediates heat sensation and pain signaling. Although an inhibitory binding site for phosphoinositides was identified at the vanilloid site in TRPV1 structures, a mechanism for phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) to both inhibit and potentiate TRPV1 activity is lacking. This gap in knowledge led us to examine structural and sequence overlap between TRPV1 and the PI(4,5)P2 binding site of TRPV5. In an adjacent space to the S6 helix we identify a second PI(4,5)P2 binding site in TRPV1, which we term the “front porch”.

Eukaryotic genomes self-organize into diverse three-dimensional (3D) chromatin conformations through intranuclear long-range interactions, yet it remains challenging to interpret how concurrent interactions combine along a chromatin polymer to shape measurable conformational readouts. Building on a minimal harmonic polymer model and the Gaussian covariance formalism, we present a 3D genome circuit representation that reorganizes the covariance-derived effective interaction strength (EIS) of a target locus pair into motif-level interaction patterns.