Mechanism of Side Chain-Controlled Proton Conductivity in Bioinspired Peptidic Nanostructures.

Bioinspired peptide assemblies are promising candidates for use as proton-conducting materials in electrochemical devices and other advanced technologies. Progress toward applications requires establishing foundational structure-function relationships for transport in these materials. This experimental-theoretical study sheds light on how the molecular structure and proton conduction are linked in three synthetic cyclic peptide nanotube assemblies that comprise the three canonical basic amino acids (lysine, arginine, and histidine).

Unique Inversion Events of Residues around the Backbone in the Turn Domain of β-Arches in Amylin Fibrils.

Orientational inversion events of residues along the turn domains of amylin fibrils have been detected. This exceptional phenomenon has been observed in isolated amylin fibrils and in the cross-seeding amylin-Aβ and amylin-NAC fibrils. These new findings provide new avenues for detection of side chain flipping and side chain inversion events in turn domains and loops of various proteins.

Effect of late endosomal DOBMP lipid and traditional model lipids of electrophysiology on the anthrax toxin channel activity.

Anthrax toxin action requires triggering of natural endocytic transport mechanisms whereby the binding component of the toxin forms channels (PA) within endosomal limiting and intraluminal vesicle membranes to deliver the toxin's enzymatic components into the cytosol. Membrane lipid composition varies at different stages of anthrax toxin internalization, with intraluminal vesicle membranes containing ~70% of anionic bis(monoacylglycero)phosphate lipid. Using model bilayer measurements, we show that membrane lipids can have a strong effect on the anthrax toxin channel properties, including the channel-forming activity, voltage-gating, conductance, selectivity, and enzymatic factor binding.

Parameterization of Palmitoylated Cysteine, Farnesylated Cysteine, Geranylgeranylated Cysteine, and Myristoylated Glycine for the Martini Force Field.

Peripheral membrane proteins go through various post-translational modifications that covalently bind fatty acid tails to specific amino acids. These post-translational modifications significantly alter the lipophilicity of the modified proteins and allow them to anchor to biological membranes. Over 1000 different proteins have been identified to date that require such membrane-protein interactions to carry out their biological functions, including members of the Src and Ras superfamilies that play key roles in cell signaling and carcinogenesis.

A minimal length rigid helical peptide motif allows rational design of modular surfactants.

Extensive work has been invested in the design of bio-inspired peptide emulsifiers. Yet, none of the formulated surfactants were based on the utilization of the robust conformation and self-assembly tendencies presented by the hydrophobins, which exhibited highest surface activity among all known proteins. Here we show that a minimalist design scheme could be employed to fabricate rigid helical peptides to mimic the rigid conformation and the helical amphipathic organization.

Molecular Mechanisms of the Bindings between Non-Amyloid β Component Oligomers and Amylin Oligomers.

It has been suggested that the connection between amyloidogenic diseases is related to the interactions between aggregates of amyloids, which are related to type 2 diabetes and Parkinson's disease. Herein, we illustrate the interactions between amylin oligomers and non-amyloid β component (NAC) oligomers. Using molecular dynamics simulations and statistical calculations, we studied the mechanisms through which NAC oligomers interact with amylin oligomers to form NAC-amylin hetero-oligomers.

Non-Amyloid-β Component of Human α-Synuclein Oligomers Induces Formation of New Aβ Oligomers: Insight into the Mechanisms That Link Parkinson's and Alzheimer's Diseases.

Parkinson's disease (PD) is characterized by the formation of Lewy bodies (LBs), of which their major component is the non-amyloid-β component (NAC) of α-synuclein (AS). Clinical studies have identified a link between PD and Alzheimer's disease (AD), but the question of why PD patients are at risk to develop various types of dementia, such as AD, is still elusive. In vivo studies have shown that Aβ can act as a seed for NAC/AS aggregation, promoting NAC/AS aggregation and thus contributing to the etiology of PD.

Theoretical Models of Generalized Quasispecies.

Theoretical modeling of quasispecies has progressed in several directions. In this chapter, we review the works of Emmanuel Tannenbaum, who, together with Eugene Shakhnovich at Harvard University and later with colleagues and students at Ben-Gurion University in Beersheva, implemented one of the more useful approaches, by progressively setting up various formulations for the quasispecies model and solving them analytically. Our review will focus on these papers that have explored new models, assumed the relevant mathematical approximations, and proceeded to analytically solve for the steady-state solutions and run stochastic simulations .

Amylin-Aβ oligomers at atomic resolution using molecular dynamics simulations: a link between Type 2 diabetes and Alzheimer's disease.

Clinical studies have identified Type 2 diabetes (T2D) as a risk factor of Alzheimer's disease (AD). One of the potential mechanisms that link T2D and AD is the loss of cells associated with degenerative changes. Amylin1-37 aggregates (the pathological species in T2D) were found to be co-localized with those of Aβ1-42 (the pathological species in AD) to form the Amylin1-37-Aβ1-42 plaques, promoting aggregation and thus contributing to the etiology of AD.

A Proposed Atomic Structure of the Self-Assembly of the Non-Amyloid-β Component of Human α-Synuclein As Derived by Computational Tools.

α-Synuclein (AS) fibrils are the major hallmarks of Parkinson's disease (PD). It is known that the central domain of the 140-residue AS protein, known as the non-amyloid-β component (NAC), plays a crucial role in aggregation. The secondary structure of AS fibrils (including the NAC domain) has been proposed on the basis of solid-state nuclear magnetic resonance studies, but the atomic structure of the self-assembly of NAC (or AS itself) is still elusive.

Spontaneous structural transition in phospholipid-inspired aromatic phosphopeptide nanostructures.

Phospholipid membranes could be considered a prime example of the ability of nature to produce complex yet ordered structures, by spontaneous and efficient self-assembly. Inspired by the unique properties and architecture of phospholipids, we designed simple amphiphilic decapeptides, intended to fold in the center of the peptide sequence, with a phosphorylated serine "head" located within a central turn segment, and two hydrophobic "tails". The molecular design also included the integration of the diphenylalanine motif, previously shown to facilitate self-assembly and increase nanostructure stability.

Orientations of residues along the β-arch of self-assembled amylin fibril-like structures lead to polymorphism.

Amylin is an endocrine hormone peptide that consists of 37 residues and is the main component of extracellular amyloid deposits found in the pancreas of most type 2 diabetes patients. Amylin peptides are self-assembled to form oligomers and fibrils. So far, four different molecular structures of the self-assembled amylin fibrils have been observed experimentally: two ssNMR models and two crystal models.

Repression/depression of conjugative plasmids and their influence on the mutation-selection balance in static environments.

We study the effect that conjugation-mediated Horizontal Gene Transfer (HGT) has on the mutation-selection balance of a population in a static environment. We consider a model whereby a population of unicellular organisms, capable of conjugation, comes to mutation-selection balance in the presence of an antibiotic, which induces a first-order death rate constant [Formula: see text] for genomes that are not resistant. We explicitly take into consideration the repression/de-repression dynamics of the conjugative plasmid, and assume that a de-repressed plasmid remains temporarily de-repressed after copying itself into another cell.