[English] 日本語
Yorodumi
- PDB-7o1q: Amyloid beta oligomer displayed on the alpha hemolysin scaffold -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7o1q
TitleAmyloid beta oligomer displayed on the alpha hemolysin scaffold
ComponentsAlpha-hemolysin hybridized Abeta
KeywordsTOXIN / Amyloid beta oligomer / alpha hemolysin / Alzheimer's Disease
Function / homology
Function and homology information


cytolysis in another organism / amyloid-beta complex / growth cone lamellipodium / cellular response to norepinephrine stimulus / collateral sprouting in absence of injury / growth cone filopodium / microglia development / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / regulation of Wnt signaling pathway ...cytolysis in another organism / amyloid-beta complex / growth cone lamellipodium / cellular response to norepinephrine stimulus / collateral sprouting in absence of injury / growth cone filopodium / microglia development / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / regulation of Wnt signaling pathway / axon midline choice point recognition / regulation of synapse structure or activity / hippocampal neuron apoptotic process / astrocyte activation involved in immune response / NMDA selective glutamate receptor signaling pathway / regulation of spontaneous synaptic transmission / mating behavior / growth factor receptor binding / peptidase activator activity / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / PTB domain binding / positive regulation of amyloid fibril formation / Golgi-associated vesicle / astrocyte projection / neuron remodeling / Lysosome Vesicle Biogenesis / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / nuclear envelope lumen / dendrite development / TRAF6 mediated NF-kB activation / positive regulation of protein metabolic process / signaling receptor activator activity / negative regulation of long-term synaptic potentiation / Advanced glycosylation endproduct receptor signaling / transition metal ion binding / The NLRP3 inflammasome / modulation of excitatory postsynaptic potential / main axon / intracellular copper ion homeostasis / regulation of multicellular organism growth / ECM proteoglycans / response to insulin-like growth factor stimulus / regulation of presynapse assembly / positive regulation of T cell migration / neuronal dense core vesicle / Purinergic signaling in leishmaniasis infection / cellular response to manganese ion / positive regulation of chemokine production / Notch signaling pathway / swimming behavior / neuron projection maintenance / extracellular matrix organization / clathrin-coated pit / positive regulation of mitotic cell cycle / axonogenesis / Mitochondrial protein degradation / positive regulation of calcium-mediated signaling / ionotropic glutamate receptor signaling pathway / platelet alpha granule lumen / astrocyte activation / response to interleukin-1 / regulation of neuron apoptotic process / cellular response to copper ion / cellular response to cAMP / positive regulation of glycolytic process / endosome lumen / trans-Golgi network membrane / positive regulation of interleukin-1 beta production / dendritic shaft / protein serine/threonine kinase binding / positive regulation of long-term synaptic potentiation / learning / central nervous system development / adult locomotory behavior / Post-translational protein phosphorylation / serine-type endopeptidase inhibitor activity / locomotory behavior / microglial cell activation / cellular response to nerve growth factor stimulus / TAK1-dependent IKK and NF-kappa-B activation / positive regulation of non-canonical NF-kappaB signal transduction / synapse organization / visual learning / recycling endosome / regulation of long-term neuronal synaptic plasticity / positive regulation of interleukin-6 production / positive regulation of JNK cascade / Golgi lumen / response to lead ion / cognition / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / cellular response to amyloid-beta / endocytosis / neuron projection development / positive regulation of tumor necrosis factor production / positive regulation of inflammatory response / calcium ion transport / Platelet degranulation / regulation of translation / heparin binding
Similarity search - Function
Aerolysin/haemolysin toxin, conserved site / Aerolysin type toxins signature. / Bi-component toxin, staphylococci / Leukocidin/Hemolysin toxin / Leukocidin/Hemolysin toxin family / Leukocidin/porin MspA superfamily / Amyloidogenic glycoprotein, copper-binding / Amyloidogenic glycoprotein, copper-binding domain conserved site / Amyloidogenic glycoprotein, copper-binding domain superfamily / Copper-binding of amyloid precursor, CuBD ...Aerolysin/haemolysin toxin, conserved site / Aerolysin type toxins signature. / Bi-component toxin, staphylococci / Leukocidin/Hemolysin toxin / Leukocidin/Hemolysin toxin family / Leukocidin/porin MspA superfamily / Amyloidogenic glycoprotein, copper-binding / Amyloidogenic glycoprotein, copper-binding domain conserved site / Amyloidogenic glycoprotein, copper-binding domain superfamily / Copper-binding of amyloid precursor, CuBD / Amyloid precursor protein (APP) copper-binding (CuBD) domain signature. / Amyloidogenic glycoprotein, heparin-binding / Amyloid A4 N-terminal heparin-binding / Amyloidogenic glycoprotein, amyloid-beta peptide superfamily / Beta-amyloid peptide (beta-APP) / Amyloidogenic glycoprotein, amyloid-beta peptide / Beta-amyloid precursor protein C-terminal / Amyloidogenic glycoprotein, intracellular domain, conserved site / Beta-amyloid precursor protein C-terminus / Amyloid precursor protein (APP) intracellular domain signature. / Amyloidogenic glycoprotein, extracellular / Amyloidogenic glycoprotein, E2 domain / E2 domain superfamily / Amyloidogenic glycoprotein, heparin-binding domain superfamily / E2 domain of amyloid precursor protein / Amyloid precursor protein (APP) E1 domain profile. / Amyloid precursor protein (APP) E2 domain profile. / amyloid A4 / Amyloidogenic glycoprotein / Proteinase inhibitor I2, Kunitz, conserved site / Pancreatic trypsin inhibitor (Kunitz) family signature. / BPTI/Kunitz family of serine protease inhibitors. / Pancreatic trypsin inhibitor Kunitz domain / Kunitz/Bovine pancreatic trypsin inhibitor domain / Pancreatic trypsin inhibitor (Kunitz) family profile. / Pancreatic trypsin inhibitor Kunitz domain superfamily / PH-like domain superfamily
Similarity search - Domain/homology
Amyloid-beta precursor protein / Alpha-hemolysin
Similarity search - Component
Biological speciesStaphylococcus aureus (bacteria)
Homo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 Å
AuthorsWu, J. / Blum, T.B. / Farrell, D.P. / DiMaio, F. / Abrahams, J.P. / Luo, J.
CitationJournal: Angew Chem Int Ed Engl / Year: 2021
Title: Cryo-electron Microscopy Imaging of Alzheimer's Amyloid-beta 42 Oligomer Displayed on a Functionally and Structurally Relevant Scaffold.
Authors: Jinming Wu / Thorsten B Blum / Daniel P Farrell / Frank DiMaio / Jan Pieter Abrahams / Jinghui Luo /
Abstract: Amyloid-β peptide (Aβ) oligomers are pathogenic species of amyloid aggregates in Alzheimer's disease. Like certain protein toxins, Aβ oligomers permeabilize cellular membranes, presumably through ...Amyloid-β peptide (Aβ) oligomers are pathogenic species of amyloid aggregates in Alzheimer's disease. Like certain protein toxins, Aβ oligomers permeabilize cellular membranes, presumably through a pore formation mechanism. Owing to their structural and stoichiometric heterogeneity, the structure of these pores remains to be characterized. We studied a functional Aβ42-pore equivalent, created by fusing Aβ42 to the oligomerizing, soluble domain of the α-hemolysin (αHL) toxin. Our data reveal Aβ42-αHL oligomers to share major structural, functional, and biological properties with wild-type Aβ42-pores. Single-particle cryo-EM analysis of Aβ42-αHL oligomers (with an overall 3.3 Å resolution) reveals the Aβ42-pore region to be intrinsically flexible. The Aβ42-αHL oligomers will allow many of the features of the wild-type amyloid oligomers to be studied that cannot be otherwise, and may be a highly specific antigen for the development of immuno-base diagnostics and therapies.
History
DepositionMar 30, 2021Deposition site: PDBE / Processing site: PDBE
Revision 1.0Apr 14, 2021Provider: repository / Type: Initial release
Revision 1.1Jun 9, 2021Group: Database references / Category: citation
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Aug 18, 2021Group: Database references / Category: citation / citation_author / database_2
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title / _citation_author.identifier_ORCID / _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.3Jul 10, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / em_admin / struct_ncs_dom_lim
Item: _em_admin.last_update / _struct_ncs_dom_lim.beg_auth_asym_id ..._em_admin.last_update / _struct_ncs_dom_lim.beg_auth_asym_id / _struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_auth_seq_id / _struct_ncs_dom_lim.end_auth_asym_id / _struct_ncs_dom_lim.end_auth_comp_id / _struct_ncs_dom_lim.end_auth_seq_id

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-12696
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Alpha-hemolysin hybridized Abeta
B: Alpha-hemolysin hybridized Abeta
C: Alpha-hemolysin hybridized Abeta
D: Alpha-hemolysin hybridized Abeta
E: Alpha-hemolysin hybridized Abeta
F: Alpha-hemolysin hybridized Abeta
G: Alpha-hemolysin hybridized Abeta


Theoretical massNumber of molelcules
Total (without water)234,2157
Polymers234,2157
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: microscopy
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area37350 Å2
ΔGint-104 kcal/mol
Surface area78810 Å2
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails (eV)
d_1ens_1chain "B"
d_2ens_1chain "A"
d_3ens_1chain "C"
d_4ens_1chain "D"
d_5ens_1chain "E"
d_6ens_1chain "F"
d_7ens_1chain "G"

NCS domain segments:

Component-ID: 1 / Ens-ID: ens_1 / Beg auth comp-ID: ALA / Beg label comp-ID: ALA / End auth comp-ID: ASN / End label comp-ID: ASN / Auth seq-ID: 1 - 293 / Label seq-ID: 1 - 293

Dom-IDAuth asym-IDLabel asym-ID
d_1BB
d_2AA
d_3CC
d_4DD
d_5EE
d_6FF
d_7GG

-
Components

#1: Protein
Alpha-hemolysin hybridized Abeta / Alpha-HL / Alpha-toxin / Beta-secretase C-terminal fragment / Beta-CTF / C99 / Alpha-hemolysin


Mass: 33459.270 Da / Num. of mol.: 7
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Staphylococcus aureus (bacteria), (gene. exp.) Homo sapiens (human)
Gene: hly, hla, APP, A4, AD1
Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)
References: UniProt: P09616, UniProt: P05067

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: Abeta42-AHL / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)
Buffer solutionpH: 8
Details: 50 mM Tris-HCl, pH 8.0, 500 mM NaCl, 250 mM imidazole and 0.38 mM DDM
SpecimenConc.: 4.83 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: GOLD
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD
Image recordingElectron dose: 55 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k)

-
Processing

Software
NameVersionClassification
phenix.real_space_refine1.18.2_3874refinement
PHENIX1.18.2_3874refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 141366 / Symmetry type: POINT
RefinementCross valid method: NONE
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
Displacement parametersBiso mean: 59.28 Å2
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.006616898
ELECTRON MICROSCOPYf_angle_d0.507722869
ELECTRON MICROSCOPYf_chiral_restr0.04652415
ELECTRON MICROSCOPYf_plane_restr0.00262968
ELECTRON MICROSCOPYf_dihedral_angle_d9.9736202
Refine LS restraints NCS
Ens-IDDom-IDAuth asym-IDRefine-IDTypeRms dev position (Å)
ens_1d_2BELECTRON MICROSCOPYNCS constraints0.00066278579845
ens_1d_3BELECTRON MICROSCOPYNCS constraints0.000698418456953
ens_1d_4BELECTRON MICROSCOPYNCS constraints0.00070515066134
ens_1d_5BELECTRON MICROSCOPYNCS constraints0.000719403174756
ens_1d_6BELECTRON MICROSCOPYNCS constraints0.000709481271454
ens_1d_7BELECTRON MICROSCOPYNCS constraints0.0007073643025

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more