Buffering capacity is determinant for restoring early α-synuclein aggregation
Marco A Saraiva1, M Helena Florêncio2
1Centro de Química Estrutural, Instituto Superior Técnico, University of Lisbon, Lisbon, Portugal.
Biophysical Chemistry
|January 23, 2022
Summary
Weak electrolytes like citrate buffer minimize alpha-synuclein aggregation near its isoelectric point. Buffering capacity influences aggregation dynamics and early aggregate dissociation, impacting Parkinson
Area of Science:
- Biochemistry
- Protein aggregation
- Neurodegenerative diseases
Background:
- Disordered proteins like alpha-synuclein (Syn) aggregate in conditions linked to Parkinson's disease.
- Electrolytes can minimize Syn aggregation, but the underlying electrostatic mechanisms are not fully understood.
Purpose of the Study:
- To investigate the role of buffering capacity in Syn aggregation using weak electrolytes.
- To elucidate the electrostatic forces driving Syn aggregation under varying pH conditions.
Main Methods:
- Monitoring Syn aggregation using light scattering techniques across a pH range (2-7).
- Utilizing citrate and tris-HCl buffers to assess the impact of buffering capacity.
- Employing ANS dye fluorescence to detect liquid-liquid phase separation.
Main Results:
- Citrate buffer, with buffering capacity, showed maximum Syn aggregation near the isoelectric point (pI=4.7).
- Tris-HCl buffer, lacking buffering capacity, induced a slow pI transition and early formation of large Syn aggregates.
- Buffering capacity promoted dissociation and re-aggregation of early Syn aggregates, while lack of it led to only dissociation.
Conclusions:
- Buffering capacity is crucial for restoring Syn aggregation by altering electrostatic forces and managing early aggregate dissociation.
- The study reveals complex dynamics of Syn aggregation influenced by buffer properties and pH.
- Liquid-liquid phase separation of Syn was observed at pH 7 under specific conditions.
