PDB-7dwv: Cryo-EM structure of amyloid fibril formed by familial prion dise...

基本情報

• 登録情報: データベース: PDB / ID: 7dwv
• タイトル: Cryo-EM structure of amyloid fibril formed by familial prion disease-related mutation E196K
• 要素: Major prion protein
• キーワード: PROTEIN FIBRIL / Amyloid fibril

機能・相同性

分子機能:

positive regulation of glutamate receptor signaling pathway / negative regulation of amyloid precursor protein catabolic process / lamin binding / regulation of glutamate receptor signaling pathway / regulation of calcium ion import across plasma membrane / aspartic-type endopeptidase inhibitor activity / glycosaminoglycan binding / ATP-dependent protein binding / regulation of potassium ion transmembrane transport / negative regulation of interleukin-17 production / NCAM1 interactions / negative regulation of dendritic spine maintenance / type 5 metabotropic glutamate receptor binding / cupric ion binding / negative regulation of protein processing / negative regulation of calcineurin-NFAT signaling cascade / dendritic spine maintenance / negative regulation of interleukin-2 production / negative regulation of T cell receptor signaling pathway / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / extrinsic component of membrane / cuprous ion binding / negative regulation of amyloid-beta formation / negative regulation of activated T cell proliferation / response to amyloid-beta / : / negative regulation of type II interferon production / negative regulation of long-term synaptic potentiation / intracellular copper ion homeostasis / positive regulation of protein targeting to membrane / long-term memory / response to cadmium ion / regulation of peptidyl-tyrosine phosphorylation / inclusion body / cellular response to copper ion / neuron projection maintenance / tubulin binding / negative regulation of protein phosphorylation / molecular condensate scaffold activity / molecular function activator activity / positive regulation of protein localization to plasma membrane / protein destabilization / protein homooligomerization / negative regulation of DNA-binding transcription factor activity / terminal bouton / cellular response to amyloid-beta / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of neuron apoptotic process / cellular response to xenobiotic stimulus / signaling receptor activity / amyloid-beta binding / protein-folding chaperone binding / postsynapse / microtubule binding / nuclear membrane / protease binding / response to oxidative stress / transmembrane transporter binding / molecular adaptor activity / postsynaptic density / learning or memory / regulation of cell cycle / cell cycle / membrane raft / copper ion binding / external side of plasma membrane / intracellular membrane-bounded organelle / dendrite / protein-containing complex binding / negative regulation of apoptotic process / Golgi apparatus / cell surface / endoplasmic reticulum / extracellular exosome / identical protein binding / plasma membrane / cytoplasm / cytosol

ドメイン・相同性:

Prion protein signature 1. / Prion protein signature 2. / Major prion protein N-terminal domain / Major prion protein bPrPp - N terminal / Prion protein / Major prion protein / Prion/Doppel protein, beta-ribbon domain / Prion/Doppel beta-ribbon domain superfamily / Prion/Doppel alpha-helical domain

構成要素:

Major prion protein

• 生物種: Homo sapiens (ヒト)
• 手法: 電子顕微鏡法 / らせん対称体再構成法 / クライオ電子顕微鏡法 / 解像度: 3.07 Å
• データ登録者: 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.
• 引用: ジャーナル: Sci Adv / 年: 2021; タイトル: Genetic prion disease-related mutation E196K displays a novel amyloid fibril structure revealed by cryo-EM.; 著者: Li-Qiang Wang / Kun Zhao / Han-Ye Yuan / Xiang-Ning Li / Hai-Bin Dang / Yeyang Ma / Qiang Wang / Chen Wang / Yunpeng Sun / Jie Chen / Dan Li / Delin Zhang / Ping Yin / Cong Liu / Yi Liang / ; 要旨: 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.

履歴

登録	2021年1月18日	登録サイト: PDBJ / 処理サイト: PDBJ
改定 1.0	2021年10月13日	Provider: repository / タイプ: Initial release

集合体

登録構造単位

A: Major prion protein

B: Major prion protein

C: Major prion protein

D: Major prion protein

E: Major prion protein

F: Major prion protein

概要:

• 138 kDa, 6 ポリマー

構成要素の詳細:

	分子量 (理論値)	分子数
合計 (水以外)	137,979	6
ポリマ－	137,979	6
非ポリマー	0	0
水	0	0

1

概要:

• 登録構造と同一
• 登録者が定義した集合体
• 根拠: microscopy

対称操作:

タイプ	名称	対称操作	数
identity operation	1_555		1

要素

#1: タンパク質

A B C D E F
Major prion protein / PrP / ASCR / PrP27-30 / PrP33-35C

詳細:

分子量: 22996.422 Da / 分子数: 6 / 変異: E196K / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PRNP, ALTPRP, PRIP, PRP / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P04156

実験情報

実験

• 実験: 手法: 電子顕微鏡法
• EM実験: 試料の集合状態: HELICAL ARRAY / ３次元再構成法: らせん対称体再構成法

試料調製

• 構成要素: 名称: Human prion E196K mutation amyloid fibril / タイプ: ORGANELLE OR CELLULAR COMPONENT / Entity ID: all / 由来: RECOMBINANT
• 由来(天然): 生物種: Homo sapiens (ヒト)
• 由来(組換発現): 生物種: Escherichia coli (大腸菌)
• 緩衝液: pH: 5
• 試料: 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES
• 急速凍結: 凍結剤: ETHANE

電子顕微鏡撮影

• 実験機器: モデル: Titan Krios / 画像提供: FEI Company
• 顕微鏡: モデル: FEI TITAN KRIOS
• 電子銃: 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM
• 電子レンズ: モード: BRIGHT FIELD
• 撮影: 電子線照射量: 64 e/Ų; フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k)

解析

• CTF補正: タイプ: NONE
• らせん対称: 回転角度/サブユニット: 179.657 ° / 軸方向距離/サブユニット: 2.40873 Å / らせん対称軸の対称性: C1
• 3次元再構成: 解像度: 3.07 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 24083 / 対称性のタイプ: HELICAL