2KTM

Solution NMR structure of H2H3 domain of ovine prion protein (residues 167-234)

2KTM の概要

• エントリーDOI: 10.2210/pdb2ktm/pdb
• 関連するPDBエントリー: 1tpx 1tqb 1xyu 1y2s
• 分子名称: Major prion protein (1 entity in total)
• 機能のキーワード: h2h3, prion protein, peptide folding, fibrilization core, cell membrane, membrane, prion, membrane protein
• 由来する生物種: Ovis aries (domestic sheep,lambs,wild sheep)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 10244.29

構造登録者

Pastore, A.,Adrover, M.,Pauwels, K.,de Chiara, C.,Prigent, S.,Rezeai, H. (登録日: 2010-02-04, 公開日: 2010-04-07, 最終更新日: 2024-10-30)

主引用文献

Adrover, M.,Pauwels, K.,Prigent, S.,de Chiara, C.,Xu, Z.,Chapuis, C.,Pastore, A.,Rezaei, H.
Prion fibrillization is mediated by a native structural element that comprises helices H2 and H3.
J.Biol.Chem., 285:21004-21012, 2010

PubMed Abstract: Aggregation and misfolding of the prion protein (PrP) are thought to be the cause of a family of lethal neurodegenerative diseases affecting humans and other animals. Although the structures of PrP from several species have been solved, still little is known about the mechanisms that lead to the misfolded species. Here, we show that the region of PrP comprising the hairpin formed by the helices H2 and H3 is a stable independently folded unit able to retain its secondary and tertiary structure also in the absence of the rest of the sequence. We also prove that the isolated H2H3 is highly fibrillogenic and forms amyloid fibers morphologically similar to those obtained for the full-length protein. Fibrillization of H2H3 but not of full-length PrP is concomitant with formation of aggregates. These observations suggest a "banana-peeling" mechanism for misfolding of PrP in which H2H3 is the aggregation seed that needs to be first exposed to promote conversion from a helical to a beta-rich structure.

PubMed: 20375014
DOI: 10.1074/jbc.M110.111815

実験手法

SOLUTION NMR