Pyroglutamylation modulates electronic properties and the conformational ensemble of the amyloid β-peptide.

Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by the formation of extracellular amyloid-β (Aβ) plaques. The underlying cause of AD is unknown, however, post-translational modifications (PTMs) of Aβ have been found in AD patients and are thought to play a role in protein aggregation. One such PTM is pyroglutamylation, which can occur at two sites in Aβ, Glu3 and Glu11.

Monomeric and dimeric states of human ZO1-PDZ2 are functional partners of the SARS-CoV-2 E protein.

The Envelope (E) protein of SARS-CoV-2 plays a key role in virus maturation, assembly, and virulence mechanisms. The E protein is characterized by the presence of a PDZ-binding motif (PBM) at its C-terminus that allows it to interact with several PDZ-containing proteins in the intracellular environment. One of the main binding partners of the SARS-CoV-2 E protein is the PDZ2 domain of ZO1, a protein with a crucial role in the formation of epithelial and endothelial tight junctions (TJs).

Effects of Familial Alzheimer's Disease Mutations on the Folding Free Energy and Dipole-Dipole Interactions of the Amyloid β-Peptide.

Familial Alzheimer's disease (FAD) mutations of the amyloid β-peptide (Aβ) are known to lead to early onset and more aggressive Alzheimer's disease. FAD mutations such as "Iowa" (D23N), "Arctic" (E22G), "Italian" (E22K), and "Dutch" (E22Q) have been shown to accelerate Aβ aggregation relative to the wild-type (WT). The mechanism by which these mutations facilitate increased aggregation is unknown, but each mutation results in a change in the net charge of the peptide.

Impact of Electronic Polarization on Preformed, β-Strand Rich Homogenous and Heterogenous Amyloid Oligomers.

Amyloids are a subset of intrinsically disordered proteins (IDPs) that self-assemble into cross-β oligomers and fibrils. The structural plasticity of amyloids leads to sampling of metastable, low-molecular-weight oligomers that contribute to cytotoxicity. Of interest are amyloid-β (Aβ) and islet amyloid polypeptide (IAPP), which are involved in the pathology of Alzheimer's disease and Type 2 Diabetes Mellitus, respectively.

Insights into Stabilizing Forces in Amyloid Fibrils of Differing Sizes from Polarizable Molecular Dynamics Simulations.

Pathological aggregation of amyloid-forming proteins is a hallmark of a number of human diseases, including Alzheimer's, type 2 diabetes, Parkinson's, and more. Despite having very different primary amino acid sequences, these amyloid proteins form similar supramolecular, fibril structures that are highly resilient to physical and chemical denaturation. To better understand the structural stability of disease-related amyloids and to gain a greater understanding of factors that stabilize functional amyloid assemblies, insights into tertiary and quaternary interactions are needed.