A comprehensive study focusing on the combined influence of the charge sequence pattern and the type of positively charged amino acids on the formation of secondary structures in sequence-specific polyampholytes is presented. The sequences of interest consisting exclusively of ionizable amino acids (lysine, K; arginine, R; and glutamic acid, E) are (EKEK)5, (EKKE)5, (ERER)5, (ERRE)5, and (EKER)5. The stability of the secondary structure was examined at three pH values in the presence of urea and NaCl. The results presented here underscore the combined prominent effects of the charge sequence pattern and the type of positively charged monomers on secondary structure formation. Additionally, (ERRE)5 readily aggregated across a wide range of pH. In contrast, sequences with the same charge pattern, (EKKE)5, as well as the sequences with the equivalent amino acid content, (ERER)5, exhibited no aggregate formation under equivalent pH and concentration conditions.

All-atom simulations populate a predicted class of misfolding, and ensembles are proposed based on structural mass spectrometry.

Biomolecules can be sequestered into membrane-less compartments, referred to as biomolecular condensates. Experimental and computational methods ha...

Cryo-electron and atomic force microscopy shed light on how fibrils of the protein tau, which accumulate in the brain of people with Alzheimer’s disease, can be disassembled by short peptides, providing a possible route towards developing treatments.

Wetting of liquid droplets on passive surfaces is ubiquitous in our daily lives, and the governing physical laws are well understood. When surfaces...

Pathological aggregation of repeat-expanded RNA is implicated in neurodegeneration. Now results demonstrate that biomolecular condensates can promote irreversible clustering of GC-rich repeat RNAs fac...

The aggregation of α-synuclein into amyloid fibrils is a hallmark of Parkinson’s disease. This process has been shown to directly involve interacti...

Nature Communications - The formation of coacervates through phase separation of oppositely charged polyelectrolytes (PEs) is critical for understanding biological condensates and developing...

Many biopolymers are highly charged, and as in the case of many polymer mixtures, they tend to phase separate as a natural consequence of chain con...

Nature Chemical Biology - Uechi et al. found that a small-molecule lipoamide dissolves stress granules (SGs) by targeting SFPQ, a redox-sensitive disordered SG protein, alleviating pathological...

CLAPM uses proximity labeling mass spectrometry to monitor proteomes within phase-separated droplets. This approach identifies condensate-specific proteins to assess proteome dynamics in various cell ...

Nature - Cryogenic electron microscopy structures of amyloid filaments extracted from patient brains reveal that the protein TAF15 forms filaments that characterize certain cases of frontotemporal...

Nuclear speckles are enriched in serine / arginine rich splicing factors (SRSFs), such as SRSF1. Splicing factors and proteins such as TDP43 concentrate into distinct speckle territories to enable pre...

Aberrant protein aggregation underlies a variety of age-related neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Little is known, however, about the molecular mechanisms th...

It is well known that peptide and protein fibrillation is strongly affected by the solution conditions, but a fundamental understanding of how amyloid fibril nucleation depends on solution pH, salt concentration, and solvent is absent. Here, we use expressions from Debye–Hückel theory to describe the interactions between charged amino acids in combination with our recently developed nonstandard nucleation theory to predict the concentration dependence of the fibril nucleation rate under different solvent conditions. The general rule that emerges from these considerations is that changes in solution pH, salt concentration, and solvent that increase the bonding energy between the fibril building blocks decrease the fibril solubility and promote fibril nucleation, in line with experimental observations. The simple analytical relations among the nucleation rate, fibril solubility, and binding energies provide a tool to controlling and understanding amyloid fibril formation by changing the solution conditions.

Multivalent proteins undergo coupled segregative and associative phase transitions. Phase separation, a segregative transition, is driven by macromolecular solubility, and this leads to coexisting pha...

Nature Chemistry - Understanding of the molecular mechanisms underlying the maturation of protein condensates into amyloid fibrils associated with neurodegenerative diseases has so far remained...

Biomolecular condensates mediate diverse cellular processes. The density-transition process of condensate formation results in the selective partition…

Nature - The structures of tau filaments from patients with the neurodegenerative disorder Pick’s disease show that the filament fold is different from that of the tau filaments found in...