1XQ8

Human micelle-bound alpha-synuclein

1XQ8 の概要

• エントリーDOI: 10.2210/pdb1xq8/pdb
• NMR情報: BMRB: 5744
• 分子名称: Alpha-synuclein (1 entity in total)
• 機能のキーワード: micelle-bound helix, lipid binding protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P37840
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14476.11

構造登録者

Ulmer, T.S.,Bax, A.,Cole, N.B.,Nussbaum, R.L. (登録日: 2004-10-11, 公開日: 2005-01-11, 最終更新日: 2024-05-22)

主引用文献

Ulmer, T.S.,Bax, A.,Cole, N.B.,Nussbaum, R.L.
Structure and dynamics of micelle-bound human alpha-synuclein
J.Biol.Chem., 280:9595-9603, 2005

PubMed Abstract: Misfolding of the protein alpha-synuclein (aS), which associates with presynaptic vesicles, has been implicated in the molecular chain of events leading to Parkinson's disease. Here, the structure and dynamics of micelle-bound aS are reported. Val3-Val37 and Lys45-Thr92 form curved alpha-helices, connected by a well ordered, extended linker in an unexpected anti-parallel arrangement, followed by another short extended region (Gly93-Lys97), overlapping the recently identified chaperone-mediated autophagy recognition motif and a highly mobile tail (Asp98-Ala140). Helix curvature is significantly less than predicted based on the native micelle shape, indicating a deformation of the micelle by aS. Structural and dynamic parameters show a reduced helical content for Ala30-Val37. A dynamic variation in interhelical distance on the microsecond timescale is complemented by enhanced sub-nanosecond timescale dynamics, particularly in the remarkably glycine-rich segments of the helices. These unusually rich dynamics may serve to mitigate the effect of aS binding on membrane fluidity. The well ordered conformation of the helix-helix connector indicates a defined interaction with lipidic surfaces, suggesting that, when bound to larger diameter synaptic vesicles, it can act as a switch between this structure and a previously proposed uninterrupted helix.

PubMed: 15615727
DOI: 10.1074/jbc.M411805200

実験手法

SOLUTION NMR