Alteration of the Conformational Dynamics of a DNA Hairpin by α-Synuclein in the Presence of Aqueous Two-Phase Systems.

Chemistry

Physical Chemistry I-Biophysical Chemistry, Faculty of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn Str. 4a, 44227, Dortmund, Germany.

Published: August 2020

AI Article Synopsis

  • The study investigates how α-synuclein, a protein linked to Parkinson's disease, impacts the structure of a specific DNA hairpin using a technique called Förster resonance energy transfer.
  • Binding of α-synuclein to the DNA hairpin's loop changes its typical open-closed states, especially in conditions that simulate cellular environments.
  • The research suggests that beyond forming harmful aggregates, α-synuclein could influence the expression of genes relevant to Parkinson's, and the findings may also shed light on how organisms in high-pressure environments function.

Article Abstract

The effect of an amyloidogenic intrinsically disordered protein, α-synuclein, which is associated with Parkinson's disease (PD), on the conformational dynamics of a DNA hairpin (DNA-HP) was studied by employing the single-molecule Förster resonance energy transfer method. The open-to-closed conformational equilibrium of the DNA-HP is drastically affected by binding of monomeric α-synuclein to the loop region of the DNA-HP. Formation of a protein-bound intermediate conformation is fostered in the presence of an aqueous two-phase system mimicking intracellular liquid-liquid phase separation. Using pressure modulation, additional mechanistic information about the binding complex could be retrieved. Hence, in addition to toxic amyloid formation, α-synuclein may alter expression profiles of disease-modifying genes in PD. Furthermore, these findings might also have significant bearings on the understanding of the physiology of organisms thriving at high pressures in the deep sea.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496936PMC
http://dx.doi.org/10.1002/chem.202002119DOI Listing

Publication Analysis

Top Keywords

conformational dynamics
8
dynamics dna
8
dna hairpin
8
presence aqueous
8
aqueous two-phase
8
alteration conformational
4
α-synuclein
4
hairpin α-synuclein
4
α-synuclein presence
4
two-phase systems
4

Similar Publications

The TRAMP complex contains two enzymatic activities essential for RNA processing upstream of the nuclear exosome. Within TRAMP, RNA is 3' polyadenylated by a subcomplex of Trf4/5 and Air1/2 and unwound 3' to 5' by Mtr4, a DExH helicase. The molecular mechanisms of TRAMP assembly and RNA shuffling between the two TRAMP catalytic sites are poorly understood.

View Article and Find Full Text PDF

Hyperpolarization-activated and cyclic nucleotide-gated (HCN) ion channels are members of the cyclic nucleotide-binding family and are crucial for regulating cellular automaticity in many excitable cells. HCN channel activation contributes to pain perception, and propofol, a widely used anesthetic, acts as an analgesic by inhibiting the voltage-dependent activity of HCN channels. However, the molecular determinants of propofol action on HCN channels remain unknown.

View Article and Find Full Text PDF

Basic Science and Pathogenesis.

Alzheimers Dement

December 2024

University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA.

Background: Reversible post-translational modifications, phosphorylation and dephosphorylation, on tau protein play a critical role in the microtubule (MT) modulation. However, abnormal tau phosphorylation, which occurs in tauopathies such as Alzheimer's disease (AD), causes the dissociation of tau from MTs. The dissociated tau then aggregates into sequent forms from soluble oligomers to paired helical filaments (PHF), and insoluble neurofibrillary tangles (NFTs), a hallmark of AD.

View Article and Find Full Text PDF

Background: Pathological tau forms from Alzheimer's disease (AD) brains act as seeds, replicating in cells and forming tau aggregates in a template-like manner. The exploration of this prion-like pathogenic mechanism has predominantly occurred in transgenic mice and cell systems that overexpress tau protein and its truncated forms with pro-aggregation mutations. However, these systems do not entirely capture the propagation kinetics and template conformational changes of various tau seeds.

View Article and Find Full Text PDF

Introduction: Vaccine platforms such as viral vectors and mRNA can accelerate vaccine development in response to newly emerging pathogens, as demonstrated during the COVID-19 pandemic. However, the differential effects of platform and antigen insert on vaccine immunogenicity remain incompletely understood. Innate immune responses induced by viral vector vaccines are suggested to have an adjuvant effect for subsequent adaptive immunity.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!