8FPT

STRUCTURE OF ALPHA-SYNUCLEIN FIBRILS DERIVED FROM HUMAN LEWY BODY DEMENTIA TISSUE

8FPT の概要

• エントリーDOI: 10.2210/pdb8fpt/pdb
• NMR情報: BMRB: 31068
• 分子名称: Alpha-synuclein (1 entity in total)
• 機能のキーワード: protein fibril, amyloid, lewy body dementia, polymorphism, parkinson, structural protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 144761.08

構造登録者

Barclay, A.M.,Dhavale, D.D.,Borcik, C.G.,Rau, M.J.,Basore, K.,Milchberg, M.H.,Warmuth, O.A.,Kotzbauer, P.T.,Rienstra, C.M.,Schwieters, C.D. (登録日: 2023-01-05, 公開日: 2023-02-22, 最終更新日: 2024-12-11)

主引用文献

Dhavale, D.D.,Barclay, A.M.,Borcik, C.G.,Basore, K.,Berthold, D.A.,Gordon, I.R.,Liu, J.,Milchberg, M.H.,O'Shea, J.Y.,Rau, M.J.,Smith, Z.,Sen, S.,Summers, B.,Smith, J.,Warmuth, O.A.,Perrin, R.J.,Perlmutter, J.S.,Chen, Q.,Fitzpatrick, J.A.J.,Schwieters, C.D.,Tajkhorshid, E.,Rienstra, C.M.,Kotzbauer, P.T.
Structure of alpha-synuclein fibrils derived from human Lewy body dementia tissue.
Nat Commun, 15:2750-2750, 2024

PubMed Abstract: The defining feature of Parkinson disease (PD) and Lewy body dementia (LBD) is the accumulation of alpha-synuclein (Asyn) fibrils in Lewy bodies and Lewy neurites. Here we develop and validate a method to amplify Asyn fibrils extracted from LBD postmortem tissue samples and use solid state nuclear magnetic resonance (SSNMR) studies to determine atomic resolution structure. Amplified LBD Asyn fibrils comprise a mixture of single protofilament and two protofilament fibrils with very low twist. The protofilament fold is highly similar to the fold determined by a recent cryo-electron microscopy study for a minority population of twisted single protofilament fibrils extracted from LBD tissue. These results expand the structural characterization of LBD Asyn fibrils and approaches for studying disease mechanisms, imaging agents and therapeutics targeting Asyn.

PubMed: 38553463
DOI: 10.1038/s41467-024-46832-5

実験手法

SOLID-STATE NMR