The inhibitory action of the chaperone BRICHOS against the α-Synuclein secondary nucleation pathway.

The complex kinetics of disease-related amyloid aggregation of proteins such as α-Synuclein (α-Syn) in Parkinson's disease and Aβ42 in Alzheimer's disease include primary nucleation, amyloid fibril elongation and secondary nucleation. The latter can be a key accelerator of the aggregation process. It has been demonstrated that the chaperone domain BRICHOS can interfere with the secondary nucleation process of Aβ42.

A structural rationale for reversible vs irreversible amyloid fibril formation from a single protein.

Reversible and irreversible amyloids are two diverging cases of protein (mis)folding associated with the cross-β motif in the protein folding and aggregation energy landscape. Yet, the molecular origins responsible for the formation of reversible vs irreversible amyloids have remained unknown. Here we provide evidence at the atomic level of distinct folding motifs for irreversible and reversible amyloids derived from a single protein sequence: human lysozyme.

Homonuclear Super-Resolution NMR Spectroscopy.

In homonuclear H NMR (nuclear magnetic resonance) spectra such as [H,H]-NOESY (Nuclear Overhauser Enhancement spectroscopy), which is a historic cornerstone spectrum for biomolecular NMR structural biology, hundreds to thousands of cross peaks are present within a square of approximately 100 ppm leading to a lot of signal overlap. Spectral resolution is thus a limiting factor for unambiguous chemical shift assignment and data interpretation for dynamics and structure elucidation. Acquiring the spectra at higher magnetic fields such as at a 1.

Controlled synthesis and characterization of porous silicon nanoparticles for dynamic nuclear polarization.

Si nanoparticles (NPs) have been actively developed as a hyperpolarized magnetic resonance imaging (MRI) contrast agent with an imaging window close to one hour. However, the progress in the development of NPs has been hampered by the incomplete understanding of their structural properties that correspond to efficient hyperpolarization buildup and long polarization decays. In this work we study dynamic nuclear polarization (DNP) of single crystal porous Si (PSi) NPs with defined doping densities ranging from nominally undoped to highly doped with boron or phosphorus.

Topological Heterogeneity of Protein Kinase C Modulators in Human T-Cells Resolved with In-Cell Dynamic Nuclear Polarization NMR Spectroscopy.

Phorbol ester analogs are a promising class of anticancer therapeutics and HIV latency reversing agents that interact with cellular membranes to recruit and activate protein kinase C (PKC) isoforms. However, it is unclear how these esters interact with membranes and how this might correlate with the biological activity of different phorbol ester analogs. Here, we have employed dynamic nuclear polarization (DNP) NMR to characterize phorbol esters in a native cellular context.

Cold reactions of He with OCS and CO: competitive kinetics and the effects of the molecular multipole moments.

The reactions of He with OCS and CO have been studied at collision energies between ∼ ⋅ 200 mK and ∼ ⋅ 30 K by merging a beam of Rydberg He atoms with rotationally cold (∼3.5 K) seeded supersonic expansions containing either OCS or CO or a mixture of OCS (mole fraction 23.2%) and CO (76.

Super-resolution NMR spectroscopy.

Spectral resolution is one of the limiting factors in nuclear magnetic resonance (NMR) spectroscopy of biological systems where signal overlap often interferes with chemical shift assignment as well as dynamics and structure analysis. This problem can be addressed in part by using higher magnetic field NMR spectrometers operating at up to 1.2 GHz H frequency to enhance the resolution proportionally with the field strength, and by deuteration in combination with transverse relaxation-optimized spectroscopy that reduces the transverse relaxation rate and proportionally the resonance linewidth of the peaks yielding higher spectral resolution.

Quantifying the Hydration-Dependent Dynamics of Cu Migration and Activity in Zeolite Omega for the Partial Oxidation of Methane.

Copper-exchanged zeolite omega (Cu-omega) is a potent material for the selective conversion of methane-to-methanol (MtM) via the oxygen looping approach. However, its performance exhibits substantial variation depending on the operational conditions. Under an isothermal temperature regime, Cu-omega demonstrates subdued activity below 230 °C, but experiences a remarkable increase in activity at 290 °C.

Frequency-Chirped Magic Angle Spinning Dynamic Nuclear Polarization Combined with Electron Decoupling.

Magic angle spinning (MAS) dynamic nuclear polarization (DNP) increases the signal intensity of solid-state nuclear magnetic resonance. DNP typically uses continuous wave (CW) microwave irradiation close to the resonance frequency of unpaired electron spins. In this study, we demonstrate that frequency-chirped microwaves improve DNP performance under MAS.

Characterization of self-templating catalytic amyloids.

Amyloid aggregates with unique periodic structures have garnered significant attention due to their association with numerous diseases, including systemic amyloidoses and the neurodegenerative diseases Parkinson's, Alzheimer's, and Creutzfeld-Jakob. However, more recent investigations have expanded our understanding of amyloids, revealing their diverse functional biological roles. Amyloids have also been proposed to have played a significant role in prebiotic molecular evolution because of their exceptional stability, spontaneous formation in a prebiotic environment, catalytic and templating abilities, and cooperative interaction with fatty acids, polysaccharides, and nucleic acids.

Probing the Stability of a β-Hairpin Scaffold after Desolvation.

Probing the structural characteristics of biomolecular ions in the gas phase following native mass spectrometry (nMS) is of great interest, because noncovalent interactions, and thus native fold features, are believed to be largely retained upon desolvation. However, the conformation usually depends heavily on the charge state of the species investigated. In this study, we combine transition metal ion Förster resonance energy transfer (tmFRET) and ion mobility-mass spectrometry (IM-MS) with molecular dynamics (MD) simulations to interrogate the β-hairpin structure of GB1p in vacuo.

High-Resolution Photoelectron Spectroscopy of the Ground and First Excited Electronic States of MgXe.

We report on the characterization of the X Σ ground and the A Π (Ω = 1/2, 3/2) and B Σ electronically excited states of MgXe. Rotationally cold MgXe in the a Π(″ = 0) metastable electronic state was generated in a laser-ablation supersonic-beam source. Following single-photon excitation from the metastable state, the vibrational structure of the X state of MgXe was measured by pulsed-field-ionization zero-kinetic-energy photoelectron spectroscopy, and the adiabatic ionization energy of the X ← a ionizing transition was determined to be /() = 37,468.

H, C, and N resonance assignments and solution structure of the N-terminal divergent calponin homology (NN-CH) domain of human intraflagellar transport protein 54.

The intraflagellar transport (IFT) machinery plays a crucial role in the bidirectional trafficking of components necessary for ciliary signaling, such as the Hedgehog, Wnt/PCR, and cAMP/PKA systems. Defects in some components of the IFT machinery cause dysfunction, leading to a wide range of human diseases and developmental disorders termed ciliopathies, such as nephronophthisis. The IFT machinery comprises three sub-complexes: BBsome, IFT-A, and IFT-B.

Design of polybenzimidazolium membranes for use in vanadium redox flow batteries.

In recent years, polybenzimidazole (PBI) membranes have been proposed for vanadium redox flow batteries (VRFBs) as an alternative to perfluoroalkylsulfonic acid membranes such as Nafion™. Despite their excellent capacity retention, PBI membranes tend to suffer from a low ionic conductivity. The formation of a polybenzimidazolium through an -alkylation of the benzimidazole core is shown to improve the ionic conductivity of the membrane, with this class of materials having found uses in alkaline fuel cell and water electrolysis systems.

Experimental and Theoretical Studies on the Reactions of Aliphatic Imines with Isocyanates.

In the context of a project aiming at the replacement of the 3-substituted β-lactam ring in classical β-lactam antibiotics by an N(3)-acyl-1,3-diazetidinone moiety, we have investigated the reaction of isocyanates with imines derived from allyl glycinate and differently substituted propionaldehydes. Imines of aromatic aldehydes with anilines have been reported to react with acyl isocyanates to give 1,3-diazetidinones or 2,3-dihydro-4H-1,3,5-oxadiazin-4-ones, via [2+2] or [4+2] cycloaddition, respectively. However, neither of these products was formed with imines derived from allyl glycinate and 2-(mono)methyl propionaldehydes.

Cell-to-cell transmitted alpha-synuclein recapitulates experimental Parkinson's disease.

Parkinson's disease is characterized by a progressive accumulation of alpha-Synuclein (αSyn) neuronal inclusions called Lewy bodies in the nervous system. Lewy bodies can arise from the cell-to-cell propagation of αSyn, which can occur via sequential steps of secretion and uptake. Here, by fusing a removable short signal peptide to the N-terminus of αSyn, we developed a novel mouse model with enhanced αSyn secretion and cell-to-cell transmission.

Time-optimized protein NMR assignment with an integrative deep learning approach using AlphaFold and chemical shift prediction.

Chemical shift assignment is vital for nuclear magnetic resonance (NMR)-based studies of protein structures, dynamics, and interactions, providing crucial atomic-level insight. However, obtaining chemical shift assignments is labor intensive and requires extensive measurement time. To address this limitation, we previously proposed ARTINA, a deep learning method for automatic assignment of two-dimensional (2D)-4D NMR spectra.

Efficient determination of the accessible conformation space of multi-domain complexes based on EPR PELDOR data.

Many proteins can adopt multiple conformations which are important for their function. This is also true for proteins and domains that are covalently linked to each other. One important example is ubiquitin, which can form chains of different conformations depending on which of its lysine side chains is used to form an isopeptide bond with the C-terminus of another ubiquitin molecule.

Chemical shift transfer: an effective strategy for protein NMR assignment with ARTINA.

Chemical shift transfer (CST) is a well-established technique in NMR spectroscopy that utilizes the chemical shift assignment of one protein (source) to identify chemical shifts of another (target). Given similarity between source and target systems (e.g.

An Analysis of Nucleotide-Amyloid Interactions Reveals Selective Binding to Codon-Sized RNA.

Interactions between RNA and proteins are the cornerstone of many important biological processes from transcription and translation to gene regulation, yet little is known about the ancient origin of said interactions. We hypothesized that peptide amyloids played a role in the origin of life and that their repetitive structure lends itself to building interfaces with other polymers through avidity. Here, we report that short RNA with a minimum length of three nucleotides binds in a sequence-dependent manner to peptide amyloids.

A Benchmark Study of Protein-Fragment Complex Structure Calculations with MR.

Protein-fragment complex structures are particularly sought after in medicinal chemistry to rationally design lead molecules. These structures are usually derived using X-ray crystallography, but the failure rate is non-neglectable. NMR is a possible alternative for the calculation of weakly interacting complexes.