3q26

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.

Structures of segments of alpha-synuclein fused to maltose-binding protein suggest intermediate states during amyloid formation., Zhao M, Cascio D, Sawaya MR, Eisenberg D, Protein Sci. 2011 Jun;20(6):996-1004. doi: 10.1002/pro.630. Epub 2011 May, 3. PMID:21462277

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Categories: Escherichia coli | Cascio, D. | Eisenberg, D. | Sawaya, M R. | Zhao, M. | Amyloid | Fusion protein | Protein fibril | Sugar binding protein