3Q26

Cyrstal structure of human alpha-synuclein (10-42) fused to maltose binding protein (MBP)

Summary for 3Q26

• Entry DOI: 10.2210/pdb3q26/pdb
• Related: 3Q25 3Q27 3Q28 3Q29
• Related PRD ID: PRD_900001
• Descriptor: Maltose-binding periplasmic protein/alpha-synuclein chimeric protein, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, GLYCEROL, ... (5 entities in total)
• Functional Keywords: fusion protein, amyloid, sugar binding protein, protein fibril
• Biological source: Escherichia coli; More
• Total number of polymer chains: 1
• Total formula weight: 45205.83

Authors

Zhao, M.,Sawaya, M.R.,Cascio, D.,Eisenberg, D. (deposition date: 2010-12-19, release date: 2011-06-01, Last modification date: 2023-09-13)

Primary citation

Zhao, M.,Cascio, D.,Sawaya, M.R.,Eisenberg, D.
Structures of segments of alpha-synuclein fused to maltose-binding protein suggest intermediate states during amyloid formation
Protein Sci., 20:996-1004, 2011

PubMed Abstract: Aggregates of the protein α-synuclein are the main component of Lewy bodies, the hallmark of Parkinson's disease. α-Synuclein aggregates are also found in many human neurodegenerative diseases known as synucleinopathies. In vivo, α-synuclein associates with membranes and adopts α-helical conformations. The details of how α-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 α-synuclein. From crystal structures of fusions between MBP and four segments of α-synuclein, we have been able to trace a virtual model of the first 72 residues of α-synuclein. Instead of a mostly α-helical conformation observed in the lipid environment, our crystal structures show α-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 α-synuclein can also form fiber-like nano-crystals or amyloid-like fibrils. Our structures suggest intermediate states during amyloid formation of α-synuclein.

PubMed: 21462277
DOI: 10.1002/pro.630

Experimental method

X-RAY DIFFRACTION (1.54 Å)