%0 Journal Article
%T Diverse Metastable Structures Formed by Small Oligomers of ¦Á-Synuclein Probed by Force Spectroscopy
%A Krishna Neupane
%A Allison Solanki
%A Iveta Sosova
%A Miro Belov
%A Michael T. Woodside
%J PLOS ONE
%D 2014
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0086495
%X Oligomeric aggregates are widely suspected as toxic agents in diseases caused by protein aggregation, yet they remain poorly characterized, partly because they are challenging to isolate from a heterogeneous mixture of species. We developed an assay for characterizing structure, stability, and kinetics of individual oligomers at high resolution and sensitivity using single-molecule force spectroscopy, and applied it to observe the formation of transient structured aggregates within single oligomers of ¦Á-synuclein, an intrinsically-disordered protein linked to Parkinson¡¯s disease. Measurements of the molecular extension as the proteins unfolded under tension in optical tweezers revealed that even small oligomers could form numerous metastable structures, with a surprisingly broad range of sizes. Comparing the structures formed in monomers, dimers and tetramers, we found that the average mechanical stability increased with oligomer size. Most structures formed within a minute, with size-dependent rates. These results provide a new window onto the complex ¦Á-synuclein aggregation landscape, characterizing the microscopic structural heterogeneity and kinetics of different pathways.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0086495