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Small angle neutron scattering: a powerful tool to study polyglutamine aggregate formation
Author(s) -
Perevozchikova Tatiana,
Stanley Christopher,
McWilliamsKoeppen Helen P.,
Berthelier Valerie
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.851.7
Subject(s) - osmolyte , radius of gyration , protein aggregation , small angle neutron scattering , biophysics , chemistry , context (archaeology) , neutron scattering , biochemistry , neutron , biology , physics , paleontology , organic chemistry , quantum mechanics , polymer
Formation and accumulation of amyloid protein aggregates in selected neurons is a hallmark of many neurodegenerative disorders, including polyglutamine (polyGln) disorders like Huntington's disease (HD). PolyGln disease proteins contain an abnormally long sequence of glutamine repeats leading to the formation of fibrillar aggregates with highly stable and organized β‐sheet structures. However, there is still an open debate as to how aggregation correlates with pathogenesis and if neuronal toxicity can be associated with early stages of protein aggregation. To investigate early aggregates and the aggregation pathway we performed small‐angle neutron scattering (SANS) on synthetic polyGln peptides. SANS is a useful technique for probing structural changes on the nanometer length‐scale in solution. Measured changes in the radius of gyration and mass per length demonstrated large‐scale structural changes occurring during aggregate growth kinetics. We also investigated the effects of protein context, glutamine length, and osmolytes on aggregation behavior. The influence of osmolytes is of particular interest since the osmotic stress created by osmolyte addition allows probing hydration and thermodynamics accompanying structural changes.