Dissecting the role of glutamine in seeding peptide aggregation.

ABSTRACT: 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 molecul

SUBMITTER: Barrera EE 

PROVIDER: S-EPMC8039506 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature