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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-4452 | |||||||||
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Title | AL amyloid fibril from a lambda 1 light chain | |||||||||
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Biological species | ![]() ![]() | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
![]() | Radamaker L / Schmidt M / Faendrich M / Fritz G | |||||||||
![]() | ![]() Title: Cryo-EM structure of a light chain-derived amyloid fibril from a patient with systemic AL amyloidosis. Authors: Lynn Radamaker / Yin-Hsi Lin / Karthikeyan Annamalai / Stefanie Huhn / Ute Hegenbart / Stefan O Schönland / Günter Fritz / Matthias Schmidt / Marcus Fändrich / ![]() Abstract: Amyloid fibrils derived from antibody light chains are key pathogenic agents in systemic AL amyloidosis. They can be deposited in multiple organs but cardiac amyloid is the major risk factor of ...Amyloid fibrils derived from antibody light chains are key pathogenic agents in systemic AL amyloidosis. They can be deposited in multiple organs but cardiac amyloid is the major risk factor of mortality. Here we report the structure of a λ1 AL amyloid fibril from an explanted human heart at a resolution of 3.3 Å which we determined using cryo-electron microscopy. The fibril core consists of a 91-residue segment presenting an all-beta fold with ten mutagenic changes compared to the germ line. The conformation differs substantially from natively folded light chains: a rotational switch around the intramolecular disulphide bond being the crucial structural rearrangement underlying fibril formation. Our structure provides insight into the mechanism of protein misfolding and the role of patient-specific mutations in pathogenicity. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 4.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 13.1 KB 13.1 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 11.4 KB | Display | ![]() |
Images | ![]() | 119.5 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6ic3MC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | |
EM raw data | ![]() Data #1: Aligned, motion-corrected micrographs of AL fibrils extracted from human heart tissue [micrographs - single frame]) |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.041 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Amyloid fibril of an antibody lambda 1 light chain
Entire | Name: Amyloid fibril of an antibody lambda 1 light chain |
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Components |
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-Supramolecule #1: Amyloid fibril of an antibody lambda 1 light chain
Supramolecule | Name: Amyloid fibril of an antibody lambda 1 light chain / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all Details: Extracted fibrils from the heart of a patient suffering from systemic AL amyloidosis |
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Source (natural) | Organism: ![]() |
Molecular weight | Experimental: 2.5 kDa/nm |
-Macromolecule #1: lambda 1 light chain fragment, residues 3-118
Macromolecule | Name: lambda 1 light chain fragment, residues 3-118 / type: protein_or_peptide / ID: 1 / Number of copies: 8 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 12.177463 KDa |
Sequence | String: VLTQPPSASG TPGQRVTISC SGRSSNIGRN LVKWYQQFPG TAPKLLIYSN DQRPSGVPDR FSGSKSGTSA SLAVSGLQSE DEADYYCAA WDATLNAWVF GGGTKLTVLS QPKAAPS |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | helical reconstruction |
Aggregation state | filament |
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Sample preparation
Buffer | pH: 7 / Component - Formula: H2O / Component - Name: distilled water |
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Grid | Model: C-flat-1.2/1.3 4C / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Atmosphere: OTHER |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 80 % / Chamber temperature: 294 K / Instrument: GATAN CRYOPLUNGE 3 Details: blotted from the backside for 4 s before plunging. |
Details | Sample in pure water, pH not determined |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Digitization - Dimensions - Width: 3838 pixel / Digitization - Dimensions - Height: 3710 pixel / Digitization - Frames/image: 1-30 / Number grids imaged: 1 / Number real images: 847 / Average exposure time: 6.0 sec. / Average electron dose: 32.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Details | Refinement strategy included global minimization and local grid search and ADP were refined. Secondary structure restraints and NCS were applied during refinement. |
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Refinement | Space: REAL / Protocol: OTHER / Overall B value: 111.4 Target criteria: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS) |
Output model | ![]() PDB-6ic3: |