3Q25

Crystal structure of human alpha-synuclein (1-19) fused to maltose binding protein (MBP)

3Q25 の概要

• エントリーDOI: 10.2210/pdb3q25/pdb
• 関連するPDBエントリー: 3Q26 3Q27 3Q28 3Q29
• 関連するBIRD辞書のPRD_ID: PRD_900001
• 分子名称: Maltose-binding periplasmic protein/alpha-synuclein chimeric protein, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: fusion protein, amyloid, sugar binding protein, protein fibril
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 44551.89

構造登録者

Zhao, M.,Sawaya, M.R.,Cascio, D.,Eisenberg, D. (登録日: 2010-12-19, 公開日: 2011-06-01, 最終更新日: 2023-09-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.9 Å)