7DWV

Cryo-EM structure of amyloid fibril formed by familial prion disease-related mutation E196K

7DWV の概要

• エントリーDOI: 10.2210/pdb7dwv/pdb
• EMDBエントリー: 30887
• 分子名称: Major prion protein (1 entity in total)
• 機能のキーワード: amyloid fibril, protein fibril
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 137978.53

構造登録者

Wang, L.Q.,Zhao, K.,Yuan, H.Y.,Li, X.N.,Dang, H.B.,Ma, Y.Y.,Wang, Q.,Wang, C.,Sun, Y.P.,Chen, J.,Li, D.,Zhang, D.L.,Yin, P.,Liu, C.,Liang, Y. (登録日: 2021-01-18, 公開日: 2021-10-13, 最終更新日: 2024-11-13)

主引用文献

Wang, L.Q.,Zhao, K.,Yuan, H.Y.,Li, X.N.,Dang, H.B.,Ma, Y.,Wang, Q.,Wang, C.,Sun, Y.,Chen, J.,Li, D.,Zhang, D.,Yin, P.,Liu, C.,Liang, Y.
Genetic prion disease-related mutation E196K displays a novel amyloid fibril structure revealed by cryo-EM.
Sci Adv, 7:eabg9676-eabg9676, 2021

PubMed Abstract: Prion diseases are caused by the conformational conversion of prion protein (PrP). Forty-two different mutations were identified in human PrP, leading to genetic prion diseases with distinct clinical syndromes. Here, we report the cryo–electron microscopy structure of an amyloid fibril formed by full-length human PrP with E196K mutation, a genetic Creutzfeldt-Jakob disease–related mutation. This mutation disrupts key interactions in the wild-type PrP fibril, forming an amyloid fibril with a conformation distinct from the wild-type PrP fibril and hamster brain–derived prion fibril. The E196K fibril consists of two protofibrils. Each subunit forms five β strands stabilized by a disulfide bond and an unusual hydrophilic cavity stabilized by a salt bridge. Four pairs of amino acids from opposing subunits form four salt bridges to stabilize the zigzag interface of the two protofibrils. Our results provide structural evidences of the diverse prion strains and highlight the importance of familial mutations in inducing different strains.

PubMed: 34516876
DOI: 10.1126/sciadv.abg9676

実験手法

ELECTRON MICROSCOPY (3.07 Å)