Allosteric regulation of the tyrosine phosphatase PTP1B by a protein-protein interaction.

The rapid identification of protein-protein interactions has been significantly enabled by mass spectrometry (MS) proteomics-based methods, including affinity purification-MS, crosslinking-MS, and proximity-labeling proteomics. While these methods can reveal networks of interacting proteins, they cannot reveal how specific protein-protein interactions alter protein function or cell signaling. For instance, when two proteins interact, there can be emergent signaling processes driven purely by the individual activities of those proteins being co-localized.

Allosteric regulation of the tyrosine phosphatase PTP1B by a protein-protein interaction.

The rapid identification of protein-protein interactions has been significantly enabled by mass spectrometry (MS) proteomics-based methods, including affinity purification-MS, crosslinking-MS, and proximity-labeling proteomics. While these methods can reveal networks of interacting proteins, they cannot reveal how specific protein-protein interactions alter protein function or cell signaling. For instance, when two proteins interact, there can be emergent signaling processes driven purely by the individual activities of those proteins being co-localized.

Predicted and Experimental NMR Chemical Shifts at Variable Temperatures: The Effect of Protein Conformational Dynamics.

NMR chemical shifts provide a sensitive probe of protein structure and dynamics but remain challenging to predict and interpret. We examine the effect of protein conformational distributions on N chemical shifts for dihydrofolate reductase (DHFR), comparing QM/MM predicted shifts with experimental shifts in solution as well as frozen distributions. Representative snapshots from MD trajectories exhibit variation in predicted N chemical shifts of up to 25 ppm.

Contribution of protein conformational heterogeneity to NMR lineshapes at cryogenic temperatures.

While low-temperature Nuclear Magnetic Resonance (NMR) holds great promise for the analysis of unstable samples and for sensitizing NMR detection, spectral broadening in frozen protein samples is a common experimental challenge. One hypothesis explaining the additional linewidth is that a variety of conformations are in rapid equilibrium at room temperature and become frozen, creating an inhomogeneous distribution at cryogenic temperatures. Here, we investigate conformational heterogeneity by measuring the backbone torsion angle (Ψ) in Dihydrofolate Reductase (DHFR) at 105 K.

Electron and Spin Delocalization in [Co Se (PEt ) ] Superatoms.

Molecular clusters can function as nanoscale atoms/superatoms, assembling into superatomic solids, a new class of solid-state materials with designable properties through modifications on superatoms. To explore possibilities on diversifying building blocks, here we thoroughly studied one representative superatom, Co Se (PEt ) . We probed its structural, electronic, and magnetic properties and revealed its detailed electronic structure as valence electrons delocalize over inorganic [Co Se ] core while ligands function as an insulated shell.

Resolution in cryogenic solid state NMR: Challenges and solutions.

NMR at cryogenic temperatures has the potential to provide rich site-specific details regarding biopolymer structure, function, and mechanistic intermediates. Broad spectral lines compared with room temperature NMR can sometimes present practical challenges. A number of hypotheses regarding the origins of line broadening are explored.

Contribution of protein conformational heterogeneity to NMR lineshapes at cryogenic temperatures.

Unlabelled: While low temperature NMR holds great promise for the analysis of unstable samples and for sensitizing NMR detection, spectral broadening in frozen protein samples is a common experimental challenge. One hypothesis explaining the additional linewidth is that a variety of conformations are in rapid equilibrium at room temperature and become frozen, creating an inhomogeneous distribution at cryogenic temperatures. Here we investigate conformational heterogeneity by measuring the backbone torsion angle (Ψ) in DHFR at 105K.

Zinc Alters the Supramolecular Organization of Nucleic Acid Complexes with Full-Length TIA1.

T-Cell Intracellular Antigen-1 (TIA1) is a 43 kDa multi-domain RNA-binding protein involved in stress granule formation during eukaryotic stress response, and has been implicated in neurodegenerative diseases including Welander distal myopathy and amyotrophic lateral sclerosis. TIA1 contains three RNA recognition motifs (RRMs), which are capable of binding nucleic acids and a C-terminal Q/N-rich prion-related domain (PRD) which has been variously described as intrinsically disordered or prion inducing and is believed to play a role in promoting liquid-liquid phase separation connected with the assembly of stress granule formation. Motivated by the fact that our prior work shows RRMs 2 and 3 are well-ordered in an oligomeric full-length form, while RRM1 and the PRD appear to phase separate, the present work addresses whether the oligomeric form is functional and competent for binding, and probes the consequences of nucleic acid binding for oligomerization and protein conformation change.

Predicted and Experimental NMR Chemical Shifts at Variable Temperatures: The Effect of Protein Conformational Dynamics.

NMR chemical shifts provide a sensitive probe of protein structure and dynamics. Prediction of shifts, and therefore interpretation of shifts, particularly for the frequently measured amidic N sites, remains a tall challenge. We demonstrate that protein N chemical shift prediction from QM/MM predictions can be improved if conformational variation is included via MD sampling, focusing on the antibiotic target, Dihydrofolate reductase (DHFR).

GTP-Bound Escherichia coli FtsZ Filaments Are Composed of Tense Monomers: a Dynamic Nuclear Polarization-Nuclear Magnetic Resonance Study Using Interface Detection.

FtsZ filaments are the major structural component of the bacterial Z ring and are drivers of bacterial division. Crystal structures for FtsZ from some Gram-positive bacteria in the presence of GTP analogs suggest the possibility of a high-energy, "tense" conformation. It remains important to elucidate whether this tense form is the dominant form in filaments.

Rotating Frame Relaxation in Magic Angle Spinning Solid State NMR, a Promising Tool for Characterizing Biopolymer Motion.

Magic angle spinning NMR rotating frame relaxation measurements provide a unique experimental window into biomolecules dynamics, as is illustrated by numerous recent applications. We discuss experimental strategies for this class of experiments, with a particular focus on systems where motion-driven modulation of the chemical shift interaction is the main mechanism for relaxation. We also explore and describe common strategies for interpreting the data sets to extract motion time scale, activation energy, and angle or order parameters from rotating frame relaxation data.

Iterative Synthesis of Contorted Macromolecular Ladders for Fast-Charging and Long-Life Lithium Batteries.

We report here an iterative synthesis of long helical perylene diimide () nanoribbons with a length up to 16 fused benzene rings. These contorted, ladder-type conjugated, and atomically precise nanoribbons show great potential as organic fast-charging and long-lifetime battery cathodes. By tuning the length of the oligomers, we can simultaneously modulate the electrical conductivity and ionic diffusivity of the material.

Clinical evaluation and resonance frequency analysis of laser-ablated titanium bone-anchored hearing implant system in children with Down Syndrome.

Objectives: To evaluate complication rates and resonance frequency analysis (RFA) of the stability of a new laser-ablated titanium Bone Anchored hearing Implant system in children with Down syndrome.

Methods: A prospective, single-subject, repeat measure, cohort study in which each participant served as their own control. Consecutive paediatric patients 4yrs- 15 years old, with a primary diagnosis of Down syndrome (trisomy 21) were implanted between January 2015-January 2020 with BHX Oticon wide implants.

A native cell membrane nanoparticles system allows for high-quality functional proteoliposome reconstitution.

Proteoliposomes mimic the cell membrane environment allowing for structural and functional membrane protein analyses as well as antigen presenting and drug delivery devices. To make proteoliposomes, purified functional membrane proteins are required. Detergents have traditionally been used for the first step in this process However, they can irreversibly denature or render membrane proteins unstable, and the necessary removal of detergents after reconstitution can decrease proteoliposome yields.

Phe-Gly motifs drive fibrillization of TDP-43's prion-like domain condensates.

Transactive response DNA-binding Protein of 43 kDa (TDP-43) assembles various aggregate forms, including biomolecular condensates or functional and pathological amyloids, with roles in disparate scenarios (e.g., muscle regeneration versus neurodegeneration).

NMR assignments for the C-terminal domain of human TDP-43.

Transactive response DNA-binding protein of 43 kDa (TDP-43) is a 414-residue protein whose aberrant aggregation is implicated in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) or frontotemporal lobar degeneration (FTLD). Intriguingly, TDP-43 has also been shown to functionally oligomerize to carry out physiological functions. TDP-43 also exists in mixed condensates or granules with other proteins (e.

NMR studies of lipid regulation of the K channel KcsA.

The membrane environment, including specific lipid characteristics, plays important roles in the folding, stability, and gating of the prokaryotic potassium channel KcsA. Here we study the effect of membrane composition on the population of various functional states of KcsA. The spectra provide support for the previous observation of copurifying phospholipids with phosphoglycerol headgroups.

Scaled recoupling of chemical shift anisotropies at high magnetic fields under MAS with interspersed C-elements.

The power of chemical shift anisotropy (CSA) measurements for probing structure and dynamics of molecules has been long recognized. NMR pulse sequences that allow measurement of CSA values in an indirect dimension of a protein correlation spectrum have been employed for aliphatic groups, but for practical reasons, carbonyl functional groups have been little studied, despite the fact that carbonyls are expected to give particularly varied and informative CSA values. Specifically, the wide spectral widths of carbonyl tensors make their measurements difficult with typically attainable spectrometer settings.

Longitudinal study of use of the pressure free, adhesive bone conducting hearing system in children at a tertiary centre.

Objectives: To assess the long-term compliance and usability of the non-implantable, adhesive bone conduction hearing aid system in children. Review of patient demographics, compliance and continued use. Identification of factors that impact on future patient selection.

Inactivation in the potassium channel KcsA.

Inactivation, the slow cessation of transmission after activation, is a general feature of potassium channels. It is essential for their function, and malfunctions in inactivation leads to numerous pathologies. The detailed mechanism for the C-type inactivation, distinct from the N-type inactivation, remains an active area of investigation.

Probing allosteric coupling in a constitutively open mutant of the ion channel KcsA using solid-state NMR.

Transmembrane allosteric coupling is a feature of many critical biological signaling events. Here we test whether transmembrane allosteric coupling controls the potassium binding affinity of the prototypical potassium channel KcsA in the context of C-type inactivation. Activation of KcsA is initiated by proton binding to the pH gate upon an intracellular drop in pH.