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Title: Citrate stabilized gold nanoparticles interfere with amyloid fibril formation: D76N and ΔN6 β2-microglobulin variants

Abstract

Here, protein aggregation including the formation of dimers and multimers in solution, underlies an array of human diseases such as systemic amyloidosis which is a fatal disease caused by misfolding of native globular proteins damaging the structure and function of affected organs. Different kind of interactors can interfere with the formation of protein dimers and multimers in solution. A very special class of interactors are nanoparticles thanks to the extremely efficient extension of their interaction surface. In particular citrate-coated gold nanoparticles (cit-AuNPs) were recently investigated with amyloidogenic protein β 2-microglobulin (β 2m). Here we present the computational studies on two challenging models known for their enhanced amyloidogenic propensity, namely ΔN6 and D76N β 2m naturally occurring variants, and disclose the role of cit-AuNPs on their fibrillogenesis. The proposed interaction mechanism lies in the interference of the cit-AuNPs with the protein dimers at the early stages of aggregation, that induces dimer disassembling. As a consequence, natural fibril formation can be inhibited. Relying on the comparison between atomistic simulations at multiple levels (enhanced sampling molecular dynamics and Brownian dynamics) and protein structural characterisation by NMR, we demonstrate that the cit-AuNPs interactors are able to inhibit protein dimer assembling. As a consequence, themore » natural fibril formation is also inhibited, as found in experiment.« less

Authors:
ORCiD logo [1]; ORCiD logo [1];  [2];  [3]; ORCiD logo [3];  [4];  [5]; ORCiD logo [6]
  1. CNR Institute Nanoscience, Modena (Italy)
  2. Univ. of Udine, Udine (Italy)
  3. Univ. of Udine, Udine (Italy); Istituto Nazionale Biostrutture e Biosistemi, Roma (Italy)
  4. Univ. di Pavia, Pavia (Italy); Istituto Nazionale Biostrutture e Biosistemi, Roma (Italy); Univ. College of London, London (United Kingdom)
  5. Univ. of Padova, Padova (Italy); CNR Institute Nanoscience, Modena (Italy)
  6. CNR Institute Nanoscience, Modena (Italy); Istituto Nazionale Biostrutture e Biosistemi, Roma (Italy); New York Univ. at Abu Dhabi, Abu Dhabi (United Arab Emirates)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1493591
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Nanoscale
Additional Journal Information:
Journal Volume: 10; Journal Issue: 10; Journal ID: ISSN 2040-3364
Publisher:
Royal Society of Chemistry
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

Brancolini, Giorgia, Maschio, Maria Celeste, Cantarutti, Cristina, Corazza, Alessandra, Fogolari, Federico, Bellotti, Vittorio, Corni, Stefano, and Esposito, Gennaro. Citrate stabilized gold nanoparticles interfere with amyloid fibril formation: D76N and ΔN6 β2-microglobulin variants. United States: N. p., 2018. Web. doi:10.1039/c7nr06808e.
Brancolini, Giorgia, Maschio, Maria Celeste, Cantarutti, Cristina, Corazza, Alessandra, Fogolari, Federico, Bellotti, Vittorio, Corni, Stefano, & Esposito, Gennaro. Citrate stabilized gold nanoparticles interfere with amyloid fibril formation: D76N and ΔN6 β2-microglobulin variants. United States. doi:10.1039/c7nr06808e.
Brancolini, Giorgia, Maschio, Maria Celeste, Cantarutti, Cristina, Corazza, Alessandra, Fogolari, Federico, Bellotti, Vittorio, Corni, Stefano, and Esposito, Gennaro. Wed . "Citrate stabilized gold nanoparticles interfere with amyloid fibril formation: D76N and ΔN6 β2-microglobulin variants". United States. doi:10.1039/c7nr06808e. https://www.osti.gov/servlets/purl/1493591.
@article{osti_1493591,
title = {Citrate stabilized gold nanoparticles interfere with amyloid fibril formation: D76N and ΔN6 β2-microglobulin variants},
author = {Brancolini, Giorgia and Maschio, Maria Celeste and Cantarutti, Cristina and Corazza, Alessandra and Fogolari, Federico and Bellotti, Vittorio and Corni, Stefano and Esposito, Gennaro},
abstractNote = {Here, protein aggregation including the formation of dimers and multimers in solution, underlies an array of human diseases such as systemic amyloidosis which is a fatal disease caused by misfolding of native globular proteins damaging the structure and function of affected organs. Different kind of interactors can interfere with the formation of protein dimers and multimers in solution. A very special class of interactors are nanoparticles thanks to the extremely efficient extension of their interaction surface. In particular citrate-coated gold nanoparticles (cit-AuNPs) were recently investigated with amyloidogenic protein β2-microglobulin (β2m). Here we present the computational studies on two challenging models known for their enhanced amyloidogenic propensity, namely ΔN6 and D76N β2m naturally occurring variants, and disclose the role of cit-AuNPs on their fibrillogenesis. The proposed interaction mechanism lies in the interference of the cit-AuNPs with the protein dimers at the early stages of aggregation, that induces dimer disassembling. As a consequence, natural fibril formation can be inhibited. Relying on the comparison between atomistic simulations at multiple levels (enhanced sampling molecular dynamics and Brownian dynamics) and protein structural characterisation by NMR, we demonstrate that the cit-AuNPs interactors are able to inhibit protein dimer assembling. As a consequence, the natural fibril formation is also inhibited, as found in experiment.},
doi = {10.1039/c7nr06808e},
journal = {Nanoscale},
number = 10,
volume = 10,
place = {United States},
year = {2018},
month = {2}
}

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