BJ Articles Ahead of Print

The protein side of the central dogma of molecular biology holds that the native state of a protein is encoded by its sequence of amino acids. For more than 50 years, this principle has been largely applied to the folding of globular proteins. Both experimental and computational biophysicists have worked to determine the thermodynamic and kinetic parameters that yield underlying principles of protein folding, as well as to develop algorithms to successfully predict structure from sequence. More recently, the biophysical community has recognized that the native states of many proteins do not involve stable globular structures, but rather disordered, dynamic conformational ensembles.

Structural dynamics of fatty acid binding proteins (FABPs), which accommodate poorly soluble ligands in the internalized binding cavities, are intimately related to their function. Recently, local unfolding of the α-helical cap in a variant of human intestinal FABP (IFABP) has been shown to correlate with the kinetics of ligand association, shedding light on the nature of the critical conformational reorganization. Yet, the physical origin and mechanism of the functionally relevant transient unfolding remain elusive.

Damage-induced retraction of axons during traumatic brain injury (TBI) is believed to play a key role in the disintegration of the neural network and eventually lead to severe symptoms such as permanent memory loss and emotional disturbances. However, fundamental questions such as how axon retraction progresses and what physical factors govern this process still remain unclear. Here, we report a combined experimental and modeling study to address these questions. Specifically, a sharp atomic force microscope (AFM) probe was used to transect axons and trigger their retraction in a precisely controlled manner.

We have used high-resolution orientation and distance measurements derived from electron paramagnetic resonance (EPR) of a bifunctional spin label (BSL) to build and refine atomistic models of protein structure. We demonstrate this approach by investigating the effects of nucleotide binding on the structure of myosin’s catalytic domain (CD), while myosin is in complex with actin. Constraints for orientation of individual helices were obtained in a previous study from continuous-wave EPR (CW-EPR) of myosin labeled at specific sites with BSL in oriented muscle fibers.

High-resolution tracking of gold nanoparticle-labeled proteins has emerged as a powerful technique for measuring the structural kinetics of processive enzymes and other biomacromolecules. These techniques use point-spread-function fitting methods borrowed from single-molecule fluorescence imaging to determine molecular positions below the diffraction limit. However, compared to fluorescence, gold nanoparticle tracking experiments are performed at significantly higher frame rates and utilize much larger probes.

Sphingolipids constitute a significant fraction of cellular plasma membrane lipid content. Among sphingolipids, ceramide levels are usually very low. However, in some cell processes like apoptosis, cell membrane ceramide levels increase markedly due to activation of enzymes like acid sphingomyelinase. This increase can change the physical state of the membrane by promoting molecular order and inducing solid ordered (So) phase domains. This effect has been observed in a previous 2H NMR study on membranes consisting of palmitoyl sphingomyelin (PSM) and palmitoyl ceramide (PCer).

A living cell’s interior is one of the most complex and intrinsically dynamic systems, providing an elaborate interplay between cytosolic crowding and ATP-driven motion, which controls cellular functionality. Here, we investigated two distinct fundamental features of the merely passive, non-bio-motor shuttled material transport within the cytoplasm of Dictyostelium discoideum cells: the anomalous non-linear scaling of the mean-squared displacement of a 150nm-diameter particle and non-Gaussian distribution of increments.

Small surface area electrodes have successfully been used to preferentially activate cutaneous nociceptors, unlike conventional large area electrodes which preferentially activate large non-nociceptor fibers. Assessments of the strength duration relationship, threshold electrotonus, and slowly increasing pulse forms have displayed different perception thresholds between large and small surface electrodes, which may indicate different excitability properties of the activated cutaneous nerves. In the current study, the origin of the differences in perception thresholds between the two electrodes was investigated.

After opening, the Shaker voltage-gated potassium (KV) channel rapidly inactivates when one of its four N-termini enters and occludes the channel pore. While it is known that the tip of the N-terminus reaches deep into the central cavity, the conformation adopted by this domain during inactivation and the nature of its interactions with the rest of the channel remain unclear. Here, we use molecular dynamics simulations coupled with electrophysiology experiments to reveal the atomic-scale mechanisms of inactivation.

Softness and rigidity of proteins are reflected in the structural dynamics, which are in turn affected by the environment. The characteristic low-frequency vibrational spectrum of a protein, known as Boson peak, is an indication of the structural rigidity of the protein at cryogenic temperature or dehydrated conditions. In this paper, the effect of hydration, temperature, and pressure on the Boson peak and volumetric properties of a globular protein are evaluated by using inelastic neutron scattering and molecular dynamics simulation.

The γ-crystallins of the eye lens nucleus are among the longest-lived proteins in the human body. Synthesized in utero, they must remain folded and soluble throughout adulthood to maintain lens transparency and avoid cataracts. γD- and γS-crystallin are two major monomeric crystallins of the human lens. γD-crystallin is concentrated in the oldest lens fiber cells, the lens nucleus, while γS-crystallin is concentrated in the younger cells of the lens cortex. The kinetic stability parameters of these two-domain proteins and their isolated domains were determined and compared.

Bacterial motility under confinement is relevant to both environmental control and spread of infection. Here, we report observations on Escherichia coli, Enterobacter sp., Pseudomonas aeruginosa, and Bacillus subtillis, when they are confined within a thin layer of water around dispersed micrometer-sized particles sprinkled over a semi-solid agar gel. In this setting, E. coli and Enterobacteria orbit around the dispersed particles. The liquid layer is shaped like a shallow tent with its height at the center set by the seeding particle and the meniscus profile set by the strong surface tension of water.