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Yorodumi- PDB-8qn6: Amyloid-beta 40 type 2 filament from the leptomeninges of individ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8qn6 | ||||||||||||
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Title | Amyloid-beta 40 type 2 filament from the leptomeninges of individual with Alzheimer's disease and cerebral amyloid angiopathy | ||||||||||||
Components | Amyloid-beta A4 protein | ||||||||||||
Keywords | PROTEIN FIBRIL / amyloid-beta / amyloid / filaments / quadruplet / Abeta40 / human brain / cryo-EM / Alzheimer's disease / cerebral amyloid angiopathy | ||||||||||||
Function / homology | Function and homology information signaling receptor activator activity / Golgi-associated vesicle / clathrin-coated pit / axonogenesis / central nervous system development / heparin binding / growth cone / perikaryon / early endosome / membrane raft ...signaling receptor activator activity / Golgi-associated vesicle / clathrin-coated pit / axonogenesis / central nervous system development / heparin binding / growth cone / perikaryon / early endosome / membrane raft / signaling receptor binding / Golgi apparatus / cell surface / endoplasmic reticulum / extracellular region / nucleus / plasma membrane Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 2.4 Å | ||||||||||||
Authors | Yang, Y. / Murzin, A.S. / Peak-Chew, S.Y. / Franco, C. / Newell, K.L. / Ghetti, B. / Goedert, M. / Scheres, S.H.W. | ||||||||||||
Funding support | United Kingdom, 3items
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Citation | Journal: Acta Neuropathol Commun / Year: 2023 Title: Cryo-EM structures of Aβ40 filaments from the leptomeninges of individuals with Alzheimer's disease and cerebral amyloid angiopathy. Authors: Yang Yang / Alexey G Murzin / Sew Peak-Chew / Catarina Franco / Holly J Garringer / Kathy L Newell / Bernardino Ghetti / Michel Goedert / Sjors H W Scheres / Abstract: We used electron cryo-microscopy (cryo-EM) to determine the structures of Aβ40 filaments from the leptomeninges of individuals with Alzheimer's disease and cerebral amyloid angiopathy. In agreement ...We used electron cryo-microscopy (cryo-EM) to determine the structures of Aβ40 filaments from the leptomeninges of individuals with Alzheimer's disease and cerebral amyloid angiopathy. In agreement with previously reported structures, which were solved to a resolution of 4.4 Å, we found three types of filaments. However, our new structures, solved to a resolution of 2.4 Å, revealed differences in the sequence assignment that redefine the fold of Aβ40 peptides and their interactions. Filaments are made of pairs of protofilaments, the ordered core of which comprises D1-G38. The different filament types comprise one, two or three protofilament pairs. In each pair, residues H14-G37 of both protofilaments adopt an extended conformation and pack against each other in an anti-parallel fashion, held together by hydrophobic interactions and hydrogen bonds between main chains and side chains. Residues D1-H13 fold back on the adjacent parts of their own chains through both polar and non-polar interactions. There are also several additional densities of unknown identity. Sarkosyl extraction and aqueous extraction gave the same structures. By cryo-EM, parenchymal deposits of Aβ42 and blood vessel deposits of Aβ40 have distinct structures, supporting the view that Alzheimer's disease and cerebral amyloid angiopathy are different Aβ proteinopathies. | ||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8qn6.cif.gz | 26.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8qn6.ent.gz | 15.2 KB | Display | PDB format |
PDBx/mmJSON format | 8qn6.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8qn6_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 8qn6_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 8qn6_validation.xml.gz | 22.4 KB | Display | |
Data in CIF | 8qn6_validation.cif.gz | 30.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qn/8qn6 ftp://data.pdbj.org/pub/pdb/validation_reports/qn/8qn6 | HTTPS FTP |
-Related structure data
Related structure data | 18508MC 8qn7C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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Noncrystallographic symmetry (NCS) | NCS oper:
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-Components
#1: Protein/peptide | Mass: 4335.852 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: B4DM00 |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: helical reconstruction |
-Sample preparation
Component | Name: Amyloid-beta 40 / Type: TISSUE / Entity ID: all / Source: NATURAL |
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Source (natural) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2400 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: -0.78 ° / Axial rise/subunit: 4.87 Å / Axial symmetry: C2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 2.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 81140 / Symmetry type: HELICAL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 7Q4B Accession code: 7Q4B / Source name: PDB / Type: experimental model | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement | Resolution: 2.4→142.85 Å / Cor.coef. Fo:Fc: 0.768 / SU B: 5.681 / SU ML: 0.127 / ESU R: 0.086 Stereochemistry target values: MAXIMUM LIKELIHOOD WITH PHASES Details: HYDROGENS HAVE BEEN USED IF PRESENT IN THE INPUT
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Solvent computation | Solvent model: PARAMETERS FOR MASK CACLULATION | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 64.292 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: 1 / Total: 582 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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