2JN5

Solution Structure of a Dodecapeptide from Alpha-Synuclein Bound with Synphilin-1

2JN5 の概要

• エントリーDOI: 10.2210/pdb2jn5/pdb
• NMR情報: BMRB: 15095
• 分子名称: Alpha-synuclein (1 entity in total)
• 機能のキーワード: alpha-synuclein, n-terminus, dodecapeptide, synphilin-1, lipid binding protein, protein fibril
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1357.70

構造登録者

Zhou, C.J.,Hu, H.Y.,Lin, D.H. (登録日: 2006-12-28, 公開日: 2008-01-22, 最終更新日: 2024-05-08)

主引用文献

Xie, Y.Y.,Zhou, C.J.,Zhou, Z.R.,Hong, J.,Che, M.X.,Fu, Q.S.,Song, A.X.,Lin, D.H.,Hu, H.Y.
Interaction with synphilin-1 promotes inclusion formation of alpha-synuclein: mechanistic insights and pathological implication.
Faseb J., 24:196-205, 2010

PubMed Abstract: alpha-Synuclein (alpha-Syn) is the major component of Lewy bodies (LBs) deposited in the brains of patients with Parkinson's disease. Synphilin-1 (Sph1) is a novel alpha-Syn-interacting protein also present in the LBs. However, the roles of alpha-Syn-Sph1 interaction in LB formation and in the related pathogenesis are still unclear. We have studied the interaction between alpha-Syn and Sph1 by biochemical and structural approaches and found that the central coiled-coil domain of Sph1 specifically interacts with the N-terminal stretch of alpha-Syn. When overexpressed in HEK 293T cells, Sph1 forms inclusions together with alpha-Syn, but the Sph1-positive inclusions cannot recruit the N-terminally truncated alpha-Syn. The central portion of Sph1 can also recruit alpha-Syn and induce inclusion formation through its coiled-coil domain. These observations demonstrate that the alpha-Syn-Sph1 interaction significantly promotes the formation of cytoplasmic alpha-Syn inclusions, which may have implications for LB formation in neural cells. We have also elucidated solution structure of the coiled-coil domain of Sph1 and its interaction with the N-terminal peptide of alpha-Syn. The specific interaction between alpha-Syn and Sph1 provides mechanistic insights into the inclusion-body formation in cells and pathological implication in Parkinson's disease.

PubMed: 19762560
DOI: 10.1096/fj.09-133082

実験手法

SOLUTION NMR