The Nâ
Terminus of α-Synuclein Forms Cu(II)-Bridged Oligomers.
Chemistry
; 21(19): 7111-8, 2015 May 04.
Article
in En
| MEDLINE
| ID: mdl-25757154
ABSTRACT
The oligomerization of α-synuclein (αSyn) is one of the defining features of Parkinson's disease. Binding of divalent copper to the Nâ
terminus of αSyn has been implicated in both its function and dysfunction. Herein, the molecular details of the Cu(II) /αSyn binding interface have been revealed using a library of synthetic 56-residue αSyn peptides containing site-specific isotopic labels. Using electron paramagnetic resonance spectroscopy, αSyn is shown to coordinate Cu(II) with high affinity via two pH-dependent coordination modes between pH 6.5-8.5. Most remarkably, the data demonstrate that the dominant mode is associated with binding to oligomers (antiparallel dimers and/or cyclic trimers) in which Cu(II) ions occupy intermolecular bridging sites. The findings provide a molecular link between Cu(II) -bound αSyn and its associated quaternary oligomeric structure.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Copper
/
Alpha-Synuclein
Limits:
Humans
Language:
En
Journal:
Chemistry
Journal subject:
QUIMICA
Year:
2015
Type:
Article