Department of Biochemistry and Structural Biology, Lund University,Lund,Sweden.
Published: January 2017
AI Article Synopsis
Article Abstract
Parkinson's disease (PD) is characterized by proteinaceous aggregates named Lewy Bodies and Lewy Neurites containing α-synuclein fibrils. The underlying aggregation mechanism of this protein is dominated by a secondary process at mildly acidic pH, as in endosomes and other organelles. This effect manifests as a strong acceleration of the aggregation in the presence of seeds and a weak dependence of the aggregation rate on monomer concentration. The molecular mechanism underlying this process could be nucleation of monomers on fibril surfaces or fibril fragmentation. Here, we aim to distinguish between these mechanisms. The nature of the secondary processes was investigated using differential sedimentation analysis, trap and seed experiments, quartz crystal microbalance experiments and super-resolution microscopy. The results identify secondary nucleation of monomers on the fibril surface as the dominant secondary process leading to rapid generation of new aggregates, while no significant contribution from fragmentation was found. The newly generated oligomeric species quickly elongate to further serve as templates for secondary nucleation and this may have important implications in the spreading of PD.
Dynamic peptide networks represent an attractive structural space of supramolecular polymers in the realm of emergent complexity. Point mutations in the peptide sequence exert profound effects over the landscapes of self-assembly with an intricate interplay among the structure-function relationships. Herein, the pathway complexity of an arginine-rich peptide is studied, FmocVFFARR derived by the mutation of minimalist amyloid-inspired peptide amphiphile FmocVFFAKK, thereby focusing on its pathway-dependent self-assembly behavior.
This review presents the current understanding of (i) spontaneous self-organization of spatial structures of protein molecules, and (ii) possible ways of chaperones' assistance to this process. Specifically, we overview the most important features of spontaneous folding of proteins (mostly, of the single-domain water-soluble globular proteins): the choice of the unique protein structure among zillions of alternatives, the nucleation of the folding process, and phase transitions within protein molecules. We consider the main experimental facts on protein folding, both in vivo and in vitro, of both kinetic and thermodynamic nature.
The fibrillation of α-synuclein (α-Syn) is considered a major contributor to Parkinson's disease (PD). Recent therapeutic measures have focused on inhibiting the fibrillation of α-Syn using various small molecules. We report here the effects of two different hydroxycinnamic acids; chlorogenic acid and sinapic acid on α-Syn fibrillation and have also discussed the mechanistic insights into their mode of modulation.
Cannabis smoke is a complex aerosol mixture, featuring characteristic monoterpenes and sesquiterpenes which are susceptible to reaction with ozone and other oxidants. These reactions form less-volatile species which can contribute to secondary organic aerosol (SOA) and ultrafine particle (UFP) formation. In this work, the reaction of ozone with cannabis smoke was observed in an environmental chamber.
State Key Lab of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Shanghai Jiao Tong University, Shanghai, 200230, P. R. China.
Chirality evolution is ubiquitous and important in nature, but achieving it in artificial systems is still challenging. Herein, the chirality evolution of supramolecular helices based on l-phenylalanine derivative (LPF) and naphthylamide derivate (NDIAPY) is achieved by the strategy of electron transfer (ET) assisted secondary nucleation. ET from LPF to NDIAPY can be triggered by 5 s UV irradiation on left-handed LPF-NDIAPY co-assemblies, leading to NDIAPY radical anions and partial disassembly of the helices.
