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Open data
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Basic information
Entry | Database: PDB / ID: 6z1o | ||||||
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Title | AL amyloid fibril from a lambda 3 light chain in conformation A | ||||||
![]() | lambda 3 immunoglobulin light chain fragment, residues 2-116 | ||||||
![]() | IMMUNE SYSTEM / amyloid / antibody / systemic amyloidosis / light chain | ||||||
Function / homology | ![]() CD22 mediated BCR regulation / immunoglobulin complex / Fc epsilon receptor (FCERI) signaling / Classical antibody-mediated complement activation / Initial triggering of complement / FCGR activation / Role of phospholipids in phagocytosis / Role of LAT2/NTAL/LAB on calcium mobilization / Scavenging of heme from plasma / FCERI mediated Ca+2 mobilization ...CD22 mediated BCR regulation / immunoglobulin complex / Fc epsilon receptor (FCERI) signaling / Classical antibody-mediated complement activation / Initial triggering of complement / FCGR activation / Role of phospholipids in phagocytosis / Role of LAT2/NTAL/LAB on calcium mobilization / Scavenging of heme from plasma / FCERI mediated Ca+2 mobilization / FCGR3A-mediated IL10 synthesis / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / Regulation of Complement cascade / antigen binding / Cell surface interactions at the vascular wall / FCERI mediated MAPK activation / FCGR3A-mediated phagocytosis / Regulation of actin dynamics for phagocytic cup formation / FCERI mediated NF-kB activation / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / adaptive immune response / Potential therapeutics for SARS / immune response / extracellular space / extracellular exosome / extracellular region / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.2 Å | ||||||
![]() | Radamaker, L. / Fandrich, M. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM reveals structural breaks in a patient-derived amyloid fibril from systemic AL amyloidosis. Authors: Lynn Radamaker / Julian Baur / Stefanie Huhn / Christian Haupt / Ute Hegenbart / Stefan Schönland / Akanksha Bansal / Matthias Schmidt / Marcus Fändrich / ![]() Abstract: Systemic AL amyloidosis is a debilitating and potentially fatal disease that arises from the misfolding and fibrillation of immunoglobulin light chains (LCs). The disease is patient-specific with ...Systemic AL amyloidosis is a debilitating and potentially fatal disease that arises from the misfolding and fibrillation of immunoglobulin light chains (LCs). The disease is patient-specific with essentially each patient possessing a unique LC sequence. In this study, we present two ex vivo fibril structures of a λ3 LC. The fibrils were extracted from the explanted heart of a patient (FOR005) and consist of 115-residue fibril proteins, mainly from the LC variable domain. The fibril structures imply that a 180° rotation around the disulfide bond and a major unfolding step are necessary for fibrils to form. The two fibril structures show highly similar fibril protein folds, differing in only a 12-residue segment. Remarkably, the two structures do not represent separate fibril morphologies, as they can co-exist at different z-axial positions within the same fibril. Our data imply the presence of structural breaks at the interface of the two structural forms. | ||||||
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 | ![]() | 162 KB | Display | ![]() |
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PDB format | ![]() | 137.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 11031MC ![]() 6z1iC M: map data used to model this data C: citing same article ( |
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Similar structure data | |
EM raw data | ![]() Data #1: Raw cryo-EM movies of AL fibrils extracted from human heart tissue [micrographs - multiframe]) |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 9431.303 Da / Num. of mol.: 6 / 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 3 immunoglobulin light chain Type: COMPLEX Details: Extracted fibrils from the explanted heart of a systemic AL amyloidosis patient 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 | Details: 40 mA / Grid material: COPPER / Grid mesh size: 400 divisions/in. / 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: 1964 |
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: -1.1 ° / Axial rise/subunit: 4.8 Å / Axial symmetry: C1 | ||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 194502 Details: manual particle picking helical start-end coordinates | ||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 11003 / Algorithm: FOURIER SPACE / Num. of class averages: 1 / Symmetry type: HELICAL | ||||||||||||||||||||||||||||||
Atomic model building | B value: 73.24 / Protocol: OTHER / Space: REAL Target criteria: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS) Details: Secondary structure restraints and NCS were applied during refinement |