Dissecting the role of glutamine in seeding peptide aggregation

Exequiel E. Barrera, Francesco Zonta*, Sergio Pantano

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


Poly glutamine and glutamine-rich peptides play a central role in a plethora of pathological aggregation events. However, biophysical characterization of soluble oligomers -the most toxic species involved in these processes- remains elusive due to their structural heterogeneity and dynamical nature. Here, we exploit the high spatio-temporal resolution of coarse-grained simulations as a computational microscope to characterize the aggregation propensity and morphology of a series of polyglutamine and glutamine-rich peptides. Comparative analysis of ab-initio aggregation pinpointed a double role for glutamines. In the first phase, glutamines mediate seeding by pairing monomeric peptides, which serve as primers for higher-order nucleation. According to the glutamine content, these low molecular-weight oligomers may then proceed to create larger aggregates. Once within the aggregates, buried glutamines continue to play a role in their maturation by optimizing solvent-protected hydrogen bonds networks.

Original languageEnglish
Pages (from-to)1595-1602
Number of pages8
JournalComputational and Structural Biotechnology Journal
Publication statusPublished - Jan 2021
Externally publishedYes


  • Coarse grained modelling
  • Molecular dynamics
  • Peptide aggregation
  • Polyglutamine diseases
  • Toxic oligomers


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