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@ARTICLE{LaRosa:874630,
      author       = {La Rosa, Carmelo and Condorelli, Marcello and Compagnini,
                      Giuseppe and Lolicato, Fabio and Milardi, Danilo and Do,
                      Trang Nhu and Karttunen, Mikko and Pannuzzo, Martina and
                      Ramamoorthy, Ayyalusamy and Fraternali, Franca and Collu,
                      Francesca and Rezaei, Human and Strodel, Birgit and Raudino,
                      Antonio},
      title        = {{S}ymmetry-breaking transitions in the early steps of
                      protein self-assembly},
      journal      = {European biophysics journal},
      volume       = {49},
      number       = {2},
      issn         = {1432-1017},
      address      = {New York},
      publisher    = {Springer},
      reportid     = {FZJ-2020-01550},
      pages        = {175 - 191},
      year         = {2020},
      abstract     = {Protein misfolding and subsequent self-association are
                      complex, intertwined processes, resulting in development of
                      a het-erogeneous population of aggregates closely related to
                      many chronic pathological conditions including Type 2
                      Diabetes Mellitus and Alzheimer’s disease. To address this
                      issue, here, we develop a theoretical model in the general
                      framework of linear stability analysis. According to this
                      model, self-assemblies of peptides with pronounced
                      conformational flexibility may become, under particular
                      conditions, unstable and spontaneously evolve toward an
                      alternating array of partially ordered and disordered
                      monomers. The predictions of the theory were verified by
                      atomistic molecular dynamics (MD) simulations of islet
                      amyloid polypeptide (IAPP) used as a paradigm of
                      aggregation-prone polypeptides (proteins). Simulations of
                      dimeric, tetrameric, and hexameric human-IAPP
                      self-assemblies at physiological electrolyte concentration
                      reveal an alternating dis-tribution of the smallest domains
                      (of the order of the peptide mean length) formed by
                      partially ordered (mainly β-strands) and disordered (turns
                      and coil) arrays. Periodicity disappears upon weakening of
                      the inter-peptide binding, a result in line with the
                      predictions of the theory. To further probe the general
                      validity of our hypothesis, we extended the simulations to
                      other peptides, the Aβ(1–40) amyloid peptide, and the
                      ovine prion peptide as well as to other proteins (SOD1
                      dimer) that do not belong to the broad class of
                      intrinsically disordered proteins. In all cases, the
                      oligomeric aggregates show an alternate distribution of
                      partially ordered and disordered monomers. We also carried
                      out Surface Enhanced Raman Scattering (SERS) measurements of
                      hIAPP as an experimental validation of both the theory and
                      in silico simulations},
      cin          = {IBI-7},
      ddc          = {570},
      cid          = {I:(DE-Juel1)IBI-7-20200312},
      pnm          = {551 - Functional Macromolecules and Complexes (POF3-551)},
      pid          = {G:(DE-HGF)POF3-551},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32123956},
      UT           = {WOS:000517713400001},
      doi          = {10.1007/s00249-020-01424-1},
      url          = {https://juser.fz-juelich.de/record/874630},
}