Structures of segments of [alpha]-synuclein fused to maltose-binding protein suggest intermediate states during amyloid formation
- UCLA
Aggregates of the protein {alpha}-synuclein are the main component of Lewy bodies, the hallmark of Parkinson's disease. {alpha}-Synuclein aggregates are also found in many human neurodegenerative diseases known as synucleinopathies. In vivo, {alpha}-synuclein associates with membranes and adopts {alpha}-helical conformations. The details of how {alpha}-synuclein converts from the functional native state to amyloid aggregates remain unknown. In this study, we use maltose-binding protein (MBP) as a carrier to crystallize segments of {alpha}-synuclein. From crystal structures of fusions between MBP and four segments of {alpha}-synuclein, we have been able to trace a virtual model of the first 72 residues of {alpha}-synuclein. Instead of a mostly {alpha}-helical conformation observed in the lipid environment, our crystal structures show {alpha}-helices only at residues 1-13 and 20-34. The remaining segments are extended loops or coils. All of the predicted fiber-forming segments based on the 3D profile method are in extended conformations. We further show that the MBP fusion proteins with fiber-forming segments from {alpha}-synuclein can also form fiber-like nano-crystals or amyloid-like fibrils. Our structures suggest intermediate states during amyloid formation of {alpha}-synuclein.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- NSFDOE - BASIC ENERGY SCIENCESNIH
- OSTI ID:
- 1023685
- Journal Information:
- Protein Sci., Vol. 20, Issue (6) ; 06, 2011
- Country of Publication:
- United States
- Language:
- ENGLISH
Similar Records
Thermodynamics imprinting reveals differential binding of metals to {alpha}-synuclein: Relevance to parkinson's disease
Structure of the toxic core of α-synuclein from invisible crystals