Mapping Surface Hydrophobicity of α-Synuclein Oligomers at the Nanoscale

• DOI: 10.1021/acs.nanolett.8b02916
• Publication Date: 2018-11-01T02:58:21Z
• Authors: Ji-Eun Lee; Jason C. Sang; Margarida Rodrigues; Alexander R. Carr; Mathew H. Horrocks; Suman De; Marie N. Bongiovanni; Patrick Flagmeier; Christopher M. Do...; David J. Wales; Steven F. Lee; David Klenerman
• Keywords: Organelle

Proteins fold into a single structural ensemble but can also misfold many diverse structures including small aggregates and fibrils, which differ in their toxicity. The aggregate surface properties play an important role how they interact with the plasma membrane cellular organelles, potentially inducing toxicity, however, these have not been measured to date due lack of suitable methods. Here, we used spectrally resolved, super-resolution imaging method combined environmentally sensitive fluorescent dye measure hydrophobicity individual formed by protein α-synuclein (αS), whose aggregation is associated Parkinson's disease. We show that soluble oligomers more hydrophobic than fibrils populates range coexisting states. Overall, our data conversion fibril-like ultimately results reduction both variation hydrophobicity. This funneling characteristic energy landscape explains observed αS may be common feature aggregating proteins.