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Published on: August 18, 2017
Vortex-induced chiral bifurcation in aggregating insulin.
1Department of Chemistry, University of Warsaw, Pasteur 1, 02-093 Warsaw, Poland. wdzwolak@chem.uw.edu.pl
Chirality
|September 17, 2010
Summary
Chiral symmetry breaking in insulin aggregation leads to amyloid fibrils with temperature-dependent superstructural chirality. This phenomenon, independent of amino acid handedness, has implications for understanding protein misfolding diseases like Alzheimer's.
Area of Science:
- Biophysics
- Structural Biology
- Biochemistry
Background:
- Chiral symmetry breaking is observed in vortex-assisted crystallization, leading to enantiomeric excess.
- Insulin aggregation involves a phase transition from soluble native protein to insoluble amyloid fibrils.
- This process is coupled with a conformational change from alpha-helical to beta-sheet structures.
Purpose of the Study:
- To summarize recent developments in chiral symmetry breaking during insulin aggregation.
- To investigate the emergence of superstructural chirality in insulin amyloid fibrils.
- To explore the implications of this phenomenon for protein misfolding diseases.
Main Methods:
- Studies of agitated solutions of aggregating insulin.
- Analysis of phase transition and conformational changes.
- Extrinsic Cotton effect measurements using thioflavin T to probe superstructural chirality.
Main Results:
- Insulin aggregation, despite being L-amino acid-based, can form amyloid fibrils with superstructural chirality.
- This chirality is independent of the inherent left-handedness of amino acid residues.
- The relative formation probability of the two optical isomers is temperature-dependent.
Conclusions:
- Insulin aggregation exhibits chiral bifurcation, forming diastereomeric amyloid superstructures.
- The observed superstructural chirality is a novel feature, distinct from inherent protein chirality.
- This finding may offer insights into the structural basis of biological activity in misfolded proteins linked to diseases like Alzheimer's.
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