Salt Bridges Regulate in Silico Dimers Formation for β2-Microglobulin Amyloidogenic Variants

Authors

  • Maria Celeste Maschio Department of Physics, University of Modena and Reggio Emilia, Via Campi 213/a, 41125 Modena, Italy
  • Giorgia Brancolini Center S3, CNR-NANO Institute of Nanoscience, Via Campi 213/A, 41125 Modena, Italy
  • Stefano Corni Center S3, CNR-NANO Institute of Nanoscience, Via Campi 213/A, 41125 Modena, Italy

DOI:

https://doi.org/10.13052/jsame2245-4551.6.003

Keywords:

amyloidosis, molecular dynamics, protein aggregation, β2-microglobulin.

Abstract

β2-microglobulin is a paradigmatic amyloidogenic protein responsible for
dialysis-related amyloidosis, a disease associated to long-term hemodialyzed
patients and characterized by accumulation of amyloid deposits in the osteoar-
ticular tissues. In the early stages of amyloid fibril formation, β2-microglobulin
associates into dimers and higher oligomers, but clarifications are still needed
for the triggering conditions, mechanisms and specificity of dimer forma-
tion. To characterize the dimeric association process, the protein-protein
interactions between three different species are investigated: namely, the
native protein and the two amyloidogenic variants ΔN6 and D76N. The
dimerization process is rationalized relying on state of the art computational
methods. A comparative mechanism for how different mutations in the three
variants can affect protein dimerization and thus fibril formation is proposed. The number of salt bridges involved at the protein-protein interface correlates
with the degree of amyloidogenicity of each individual species. The findings
can offer possible strategies in controlling the dimerization mechanism based
on different β2-microglobulin protein mutations, which have significant roles
in the fibrillogenical process.

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Author Biographies

Maria Celeste Maschio, Department of Physics, University of Modena and Reggio Emilia, Via Campi 213/a, 41125 Modena, Italy

Maria Celeste Maschio is a PhD student at the University of Modena and
Reggio Emilia, Italy. She is working on a project about the modeling of
an amyloidogenic protein in solution and on nanostructures, using classical
molecular dynamics, under the supervision of Prof. Stefano Corni and Giorgia
Brancolini. She spent a period of six months in King’s College London
(UK) working with Prof. Carla Molteni on enhanced sampling methods as
Metadynamics.

Giorgia Brancolini, Center S3, CNR-NANO Institute of Nanoscience, Via Campi 213/A, 41125 Modena, Italy

Giorgia Brancolini received her Ph.D. in Chemistry from the University
of Modena and Reggio Emilia, Italy, in cooperation with the University of
Ulm, Germany. She was a post-doctoral fellow at Politecnico di Milano from
2002–2004 in the Dept. of Chemical Engineering. From 2004–2010 she was a
senior post-doctoral fellow at National Research Council in Italy. Since 2010
Dr. Brancolini is a fixed term research scientist at the Center S3 CNR-NANO
of the Institute of Nanoscience of the National Research Council in Modena,
Italy. She is working on multi scale simulations, spanning from ab initio to
classical and coarse grained models, of the interactions between proteins and
inorganic surfaces/nanoparticles.

Stefano Corni, Center S3, CNR-NANO Institute of Nanoscience, Via Campi 213/A, 41125 Modena, Italy

Stefano Corni is full-professor of Physical Chemistry at the Dept. of Chem-
ical Sciences, University of Padova, Italy, and a research associate with
CNR-NANO Modena, Italy. He got his Ph.D. in Chemistry from the Scuola
Normale Superiore di Pisa, Italy, in 2003. He is working on the classical
and quantum mechanical modeling of the interactions between proteins
and inorganic surfaces/nanoparticles, on the optical properties of molecules
interacting with metal nanoparticles and on electron transfer in biomolecules
and between biomolecules and electrodes.

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Published

2023-03-18

How to Cite

Maschio, M. C., Brancolini, G., & Corni, S. (2023). Salt Bridges Regulate in Silico Dimers Formation for β2-Microglobulin Amyloidogenic Variants. Journal of Self Assembly and Molecular Electronics, 6(1), 35–60. https://doi.org/10.13052/jsame2245-4551.6.003

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2018: Vol 6 Iss1 2018

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