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

Basic information

• Entry: Database: SASBDB / ID: SASDCJ2

Sample

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

Function / homology

Function:

Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / negative regulation of amyloid precursor protein catabolic process / regulation of glutamate receptor signaling pathway / lamin binding / aspartic-type endopeptidase inhibitor activity / regulation of calcium ion import across plasma membrane / positive regulation of glutamate receptor signaling pathway / glycosaminoglycan binding / ATP-dependent protein binding / type 5 metabotropic glutamate receptor binding / negative regulation of interleukin-17 production / cupric ion binding / negative regulation of dendritic spine maintenance / regulation of potassium ion transmembrane transport / nucleobase-containing compound metabolic process / negative regulation of calcineurin-NFAT signaling cascade / negative regulation of interleukin-2 production / negative regulation of T cell receptor signaling pathway / negative regulation of activated T cell proliferation / negative regulation of amyloid-beta formation / cuprous ion binding / 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 / response to cadmium ion / side of membrane / cellular response to copper ion / inclusion body / neuron projection maintenance / positive regulation of calcium-mediated signaling / molecular function activator activity / positive regulation of protein localization to plasma membrane / molecular condensate scaffold activity / protein destabilization / protein homooligomerization / terminal bouton / cellular response to amyloid-beta / positive regulation of neuron apoptotic process / cellular response to xenobiotic stimulus / signaling receptor activity / regulation of protein localization / protein-folding chaperone binding / amyloid-beta binding / protease binding / microtubule binding / nuclear membrane / molecular adaptor activity / response to oxidative stress / transmembrane transporter binding / learning or memory / postsynaptic density / intracellular signal transduction / membrane raft / copper ion binding / dendrite / negative regulation of apoptotic process / protein-containing complex binding / cell surface / endoplasmic reticulum / negative regulation of transcription by RNA polymerase II / Golgi apparatus / metal ion binding / identical protein binding / membrane / plasma membrane / cytosol

Domain/homology:

Prion, copper binding octapeptide repeat / Copper binding octapeptide repeat region / Major prion protein N-terminal domain / Major prion protein bPrPp - N terminal / Prion protein signature 1. / Prion protein signature 2. / Prion protein / Major prion protein / Prion/Doppel protein, beta-ribbon domain / Prion/Doppel beta-ribbon domain superfamily / Prion/Doppel alpha-helical domain

Component:

Major prion protein

• Biological species: Mus musculus (house mouse); Homo sapiens (human)
• Citation: Journal: Biophys J / Year: 2015; Title: Prion Protein-Antibody Complexes Characterized by Chromatography-Coupled Small-Angle X-Ray Scattering.; Authors: Lester Carter / Seung Joong Kim / Dina Schneidman-Duhovny / Jan Stöhr / Guillaume Poncet-Montange / Thomas M Weiss / Hiro Tsuruta / Stanley B Prusiner / Andrej Sali / ; Abstract: 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).

Contact author

• Dina Schneidman (The Hebrew University of Jerusalem)

Models

• Model #1168: ; Type: atomic / Radius of dummy atoms: 1.90 A / Chi-square value: 1.27153004943 / P-value: 0.058000; Search similar-shape structures of this assembly by Omokage search (details)
• Model #1169: ; Type: atomic / Radius of dummy atoms: 1.90 A / Chi-square value: 1.27153004943 / P-value: 0.058000; Search similar-shape structures of this assembly by Omokage search (details)
• Model #1167: ; Type: atomic / Radius of dummy atoms: 1.90 A / Chi-square value: 4.55590410686; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: Solution structure of recombinant prion protein (89–230) in complex with Fab-P; Specimen concentration: 1.00-3.70 / Entity id: 606 / 607
• Buffer: Name: sodium acetate buffer (20 mM sodium acetate, pH 5.1; 150 mM NaCl); pH: 5.1

Entity #606

Name: prion / Type: protein / Description: Major prion protein / Formula weight: 22.932 / Num. of mol.: 1 / Source: Mus musculus / References: UniProt: P04925
Sequence:

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

Entity #607

Name: Fab-P / Type: protein / Description: P-Clone Fab, Chimera / Formula weight: 47.386 / Num. of mol.: 1 / Source: Homo sapiens
Sequence:

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

Experimental information

• Beam: Instrument name: Stanford Synchrotron Radiation Lightsource (SSRL) BL4-2; City: Stanford, CA / 国: USA / Type of source: X-ray synchrotron / Wavelength: 0.113 Å / Dist. spec. to detc.: 1.7 mm
• Detector: Name: Rayonix MX225-HE

Scan

Title: Solution structure of recombinant prion protein (89–230) in complex with Fab-P
Measurement date: Dec 5, 2013 / Storage temperature: 4 °C / Cell temperature: 9.8 °C / Exposure time: 1 sec. / Number of frames: 10 / Unit: 1/A /

	Min	Max
Q	0.0124	0.4724

Distance distribution function P(R)

Sofotware P(R): GNOM 5.0 / Number of points: 498 /

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

Result

Type of curve: merged /

	Experimental	Porod
MW	73.8 kDa	-
Volume	-	106 nm3

	P(R)	P(R) error	Guinier	Guinier error
Forward scattering, I0	1066	2.78	1087.12	9.23
Radius of gyration, Rg	3.83 nm	0.13	3.92 nm	0.02

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