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Open data
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Basic information
Entry | Database: PDB / ID: 7nsl | ||||||
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Title | AL amyloid fibril from a lambda 1 light chain | ||||||
![]() | Amyloid lambda1 light chain | ||||||
![]() | IMMUNE SYSTEM / amyloid / antibody / systemic amyloidosis / light chain | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.1 Å | ||||||
![]() | Karimi Farsijani, S. / Radamaker, L. / Fandrich, M. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Role of mutations and post-translational modifications in systemic AL amyloidosis studied by cryo-EM. Authors: Lynn Radamaker / Sara Karimi-Farsijani / Giada Andreotti / Julian Baur / Matthias Neumann / Sarah Schreiner / Natalie Berghaus / Raoul Motika / Christian Haupt / Paul Walther / Volker ...Authors: Lynn Radamaker / Sara Karimi-Farsijani / Giada Andreotti / Julian Baur / Matthias Neumann / Sarah Schreiner / Natalie Berghaus / Raoul Motika / Christian Haupt / Paul Walther / Volker Schmidt / Stefanie Huhn / Ute Hegenbart / Stefan O Schönland / Sebastian Wiese / Clarissa Read / Matthias Schmidt / Marcus Fändrich / ![]() Abstract: Systemic AL amyloidosis is a rare disease that is caused by the misfolding of immunoglobulin light chains (LCs). Potential drivers of amyloid formation in this disease are post-translational ...Systemic AL amyloidosis is a rare disease that is caused by the misfolding of immunoglobulin light chains (LCs). Potential drivers of amyloid formation in this disease are post-translational modifications (PTMs) and the mutational changes that are inserted into the LCs by somatic hypermutation. Here we present the cryo electron microscopy (cryo-EM) structure of an ex vivo λ1-AL amyloid fibril whose deposits disrupt the ordered cardiomyocyte structure in the heart. The fibril protein contains six mutational changes compared to the germ line and three PTMs (disulfide bond, N-glycosylation and pyroglutamylation). Our data imply that the disulfide bond, glycosylation and mutational changes contribute to determining the fibril protein fold and help to generate a fibril morphology that is able to withstand proteolytic degradation inside the body. | ||||||
History |
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Structure visualization
Movie |
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 176.5 KB | Display | ![]() |
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PDB format | ![]() | 150.3 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 947.1 KB | Display | ![]() |
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Full document | ![]() | 949.5 KB | Display | |
Data in XML | ![]() | 29.9 KB | Display | |
Data in CIF | ![]() | 42.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 12570MC M: map data used to model this data C: citing same article ( |
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Similar structure data | |
EM raw data | ![]() Data size: 495.9 Data #1: Unaligned multi-frame micrographs of AL amyloidosis extracted ex vivo amyloid fibrils patient FOR001 [micrographs - multiframe]) |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
#1: Antibody | Mass: 12122.354 Da / Num. of mol.: 7 / Source method: isolated from a natural source / Source: (natural) ![]() |
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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 |
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Sample preparation
Component | Name: Amyloid fibril of an antibody lambda 1 immunoglobulin light chain Type: COMPLEX Details: Extracted fibrils from the explanted heart of a patient suffering from systemic AL amyloidosis Entity ID: all / Source: NATURAL |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
Buffer solution | pH: 7 |
Buffer component | Name: Distilled water / Formula: H2O |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: Sample in pure water, pH not determined |
Specimen support | Grid material: COPPER / Grid type: C-flat-1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK III / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 295 K / Details: blot for 9s before plunging |
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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: ![]() |
Electron lens | Mode: BRIGHT FIELD / Cs: 2.7 mm |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 40 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 3032 |
EM imaging optics | Energyfilter slit width: 20 eV |
Image scans | Width: 3838 / Height: 3710 / Movie frames/image: 40 |
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Processing
EM software |
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Image processing | Details: Motion-corrected and dose-weighted movie frames | ||||||||||||||||||||||||||||||
CTF correction | Details: CTF was estimated from the non-dose-weighted micrographs Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: -1.45566 ° / Axial rise/subunit: 4.76311 Å / Axial symmetry: C1 | ||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 43308 Details: manual particle picking helical start-end coordinates | ||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 43308 / Symmetry type: HELICAL | ||||||||||||||||||||||||||||||
Atomic model building | Protocol: OTHER / Space: REAL Target criteria: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS) Details: Secondary structure restraints and NCS were applied during refinement |