English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Protein aggregation including the formation of dimers and multimers insolution, underlies an array of human diseases such as systemic amyloidosiswhich is a fatal disease caused by misfolding of native globular proteinsdamaging the structure and function of affected organs. Different kind ofinteractors can interfere with the formation of protein dimers and multimers insolution. A very special class of interactors are nanoparticles thanks to theextremely efficient extension of their interaction surface. In particularcitrate-coated gold nanoparticles (cit-AuNPs) were recently investigated withamyloidogenic protein $\beta$2-microglobulin ($\beta$2m). Here we present thecomputational studies on two challenging models known for their enhancedamyloidogenic propensity, namely $\Delta$N6 and D76N $\beta$2m naturallyoccurring variants, and disclose the role of cit-AuNPs on theirfibrillogenesis. The proposed interaction mechanism lies in the interference ofthe cit-AuNPs with the protein dimers at the early stages of aggregation, thatinduces dimer disassembling. As a consequence, natural fibril formation can beinhibited. Relying on the comparison between atomistic simulations at multiplelevels (enhanced sampling molecular dynamics and Brownian dynamics) and proteinstructural characterisation by NMR, we demonstrate that the cit-AuNPsinteractors are able to inhibit protein dimer assembling. As a consequence, thenatural fibril formation is also inhibited, as found in experiment.

Citrate stabilized gold nanoparticles interfere with amyloid fibril formation: D76N and {\Delta}N6 \b{eta}2-microglobulin variants