SASDCJ2: Solution structure of recombinant prion protein (89–230) in compl...

基本情報

• 登録情報: データベース: SASBDB / ID: SASDCJ2

試料

Solution structure of recombinant prion protein (89–230) in complex with Fab-P

• Major prion protein (protein), prion, Mus musculus
• P-Clone Fab, Chimera (protein), Fab-P, Homo sapiens

機能・相同性

分子機能:

Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / 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 / negative regulation of dendritic spine maintenance / type 5 metabotropic glutamate receptor binding / cupric ion binding / nucleobase-containing compound metabolic process / response to copper ion / negative regulation of calcineurin-NFAT signaling cascade / negative regulation of interleukin-2 production / negative regulation of T cell receptor signaling pathway / activation of protein kinase activity / 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 / side of membrane / response to cadmium ion / regulation of peptidyl-tyrosine phosphorylation / inclusion body / cellular response to copper ion / neuron projection maintenance / 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 / regulation of protein localization / 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 / microtubule binding / nuclear membrane / protease binding / response to oxidative stress / transmembrane transporter binding / molecular adaptor activity / postsynaptic density / learning or memory / membrane raft / copper ion binding / dendrite / protein-containing complex binding / negative regulation of apoptotic process / Golgi apparatus / cell surface / endoplasmic reticulum / identical protein binding / membrane / metal ion binding / plasma membrane / 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: Mus musculus (ハツカネズミ); Homo sapiens (ヒト)
• 引用: ジャーナル: Biophys J / 年: 2015; タイトル: Prion Protein-Antibody Complexes Characterized by Chromatography-Coupled Small-Angle X-Ray Scattering.; 著者: Lester Carter / Seung Joong Kim / Dina Schneidman-Duhovny / Jan Stöhr / Guillaume Poncet-Montange / Thomas M Weiss / Hiro Tsuruta / Stanley B Prusiner / Andrej Sali / ; 要旨: Aberrant self-assembly, induced by structural misfolding of the prion proteins, leads to a number of neurodegenerative disorders. In particular, misfolding of the mostly α-helical cellular prion protein (PrP(C)) into a β-sheet-rich disease-causing isoform (PrP(Sc)) is the key molecular event in the formation of PrP(Sc) aggregates. The molecular mechanisms underlying the PrP(C)-to-PrP(Sc) conversion and subsequent aggregation remain to be elucidated. However, in persistently prion-infected cell-culture models, it was shown that treatment with monoclonal antibodies against defined regions of the prion protein (PrP) led to the clearing of PrP(Sc) in cultured cells. To gain more insight into this process, we characterized PrP-antibody complexes in solution using a fast protein liquid chromatography coupled with small-angle x-ray scattering (FPLC-SAXS) procedure. High-quality SAXS data were collected for full-length recombinant mouse PrP [denoted recPrP(23-230)] and N-terminally truncated recPrP(89-230), as well as their complexes with each of two Fab fragments (HuM-P and HuM-R1), which recognize N- and C-terminal epitopes of PrP, respectively. In-line measurements by fast protein liquid chromatography coupled with SAXS minimized data artifacts caused by a non-monodispersed sample, allowing structural analysis of PrP alone and in complex with Fab antibodies. The resulting structural models suggest two mechanisms for how these Fabs may prevent the conversion of PrP(C) into PrP(Sc).

登録者

• Dina Schneidman (The Hebrew University of Jerusalem)

モデル

• モデル #1168: ; タイプ: atomic / ダミー原子の半径: 1.90 A / カイ2乗値: 1.27153004943 / P-value: 0.058000; Omokage検索でこの集合体の類似形状データを探す (詳細)
• モデル #1169: ; タイプ: atomic / ダミー原子の半径: 1.90 A / カイ2乗値: 1.27153004943 / P-value: 0.058000; Omokage検索でこの集合体の類似形状データを探す (詳細)
• モデル #1167: ; タイプ: atomic / ダミー原子の半径: 1.90 A / カイ2乗値: 4.55590410686; Omokage検索でこの集合体の類似形状データを探す (詳細)

試料

• 試料: 名称: Solution structure of recombinant prion protein (89–230) in complex with Fab-P; 試料濃度: 1.00-3.70 / Entity id: 606 / 607
• バッファ: 名称: sodium acetate buffer (20 mM sodium acetate, pH 5.1; 150 mM NaCl); pH: 5.1

要素 #606

名称: prion / タイプ: protein / 記述: Major prion protein / 分子量: 22.932 / 分子数: 1 / 由来: Mus musculus / 参照: UniProt: P04925
配列:

KKRPKPGGWN TGGSRYPGQG SPGGNRYPPQ GGTWGQPHGG GWGQPHGGSW GQPHGGSWGQ PHGGGWGQGG GTHNQWNKPS KPKTNLKHVA GAAAAGAVVG GLGGYMLGSA MSRPMIHFGN DWEDRYYREN MYRYPNQVYY RPVDQYSNQN NFVHDCVNIT IKQHTVTTTT KGENFTETDV KMMERVVEQM CVTQYQKESQ AYYDGRRS

要素 #607

名称: Fab-P / タイプ: protein / 記述: P-Clone Fab, Chimera / 分子量: 47.386 / 分子数: 1 / 由来: Homo sapiens
配列:

ATQAYAELVM TQTPSSLSAS LGERVSLTCR ASQDIGNNLN WIQQKPDGTI KRLIYATSSL DSGVPKRFSG SRSGSDYSLT ISSLESEDFA DYYCLQHDTF PLTFGGGTKL EIKRTVAAPS VFIFPPSDEQ LKSGTASVVC LLNNFYPREA KVQWKVDNAL QSGNSQESVT EQDSKDSTYS LSSTLTLSKA DYEKHKVYAC EVTHQGLSSP VTKSFNRAYA EVQLLEQSGA ELVKPGASVK LSCTASGFNI EDSYIHWVKQ RPEQGLEWIG RIDPEDGETK YAPKFQGKAT ITADTSSNTA YLHLRRLTSE DTAIYYCGRG AYYIKEDFWG QGTTLTVSSA STKGPSVFPL APSSKAGGTA ALGCLVKDYF PEPVTVSWNS GALTSGVHTF PAVLQSSGLY SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VDKKVEPA

実験情報

• ビーム: 設備名称: Stanford Synchrotron Radiation Lightsource (SSRL) BL4-2; 地域: Stanford, CA / 国: USA / 線源: X-ray synchrotron / 波長: 0.113 Å / スペクトロメータ・検出器間距離: 1.7 mm
• 検出器: 名称: Rayonix MX225-HE

スキャン

タイトル: Solution structure of recombinant prion protein (89–230) in complex with Fab-P
測定日: 2013年12月5日 / 保管温度: 4 °C / セル温度: 9.8 °C / 照射時間: 1 sec. / フレーム数: 10 / 単位: 1/A /

	Min	Max
Q	0.0124	0.4724

距離分布関数 P(R)

ソフトウェア P(R): GNOM 5.0 / ポイント数: 498 /

	Min	Max
Q	0.0124103	0.472414
P(R) point	1	498
R	0	145

結果

カーブのタイプ: merged /

	実験値	Porod
分子量	73.8 kDa	-
体積	-	106 nm3

	P(R)	P(R) error	Guinier	Guinier error
前方散乱 I0	1066	2.78	1087.12	9.23
慣性半径, Rg	3.83 nm	0.13	3.92 nm	0.02

	Min	Max	Error
D	-	14.5	0.5
Guinier point	4	15	-