Sensitivity of secondary structure propensities to sequence differences between α‐ and γ‐synuclein: Implications for fibrillation

The synucleins are a family of intrinsically disordered proteins involved in various human diseases. alpha-Synuclein has been extensively characterized due to its role in Parkinson's disease where it forms intracellular aggregates, while gamma-synuclein is overexpressed in a majority of late-stage breast cancers. Despite fairly strong sequence similarity between the amyloid-forming regions of alpha- and gamma-synuclein, gamma-synuclein has only a weak propensity to form amyloid fibrils. We hypothesize that the different fibrillation tendencies of alpha- and gamma-synuclein may be related to differences in structural propensities. Here we have measured chemical shifts for gamma-synuclein and compared them to…

• UO
  University of Toronto
• CI
  Canadian Institutes of Health Research