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- EMDB-16780: CryoEM structure of AL55 amyloid fibrils extracted from the kidne... -

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Basic information

Entry
Database: EMDB / ID: EMD-16780
TitleCryoEM structure of AL55 amyloid fibrils extracted from the kidney of an AL amyloidosis patient.
Map data
Sample
  • Complex: Renal AL55 amyloid fibrils
    • Protein or peptide: Immunoglobulin lambda light chain
KeywordsLight chains / Amyloid fibrils / AL amyloidosis. / PROTEIN FIBRIL
Biological speciesHomo sapiens (human)
Methodhelical reconstruction / cryo EM / Resolution: 4.0 Å
AuthorsPuri S / Schulte T / Chaves-Sanjuan A / Ricagno S
Funding support Italy, 1 items
OrganizationGrant numberCountry
Other government20207XLJB2 Italy
CitationJournal: J Mol Biol / Year: 2023
Title: The Cryo-EM STRUCTURE of Renal Amyloid Fibril Suggests Structurally Homogeneous Multiorgan Aggregation in AL Amyloidosis.
Authors: Sarita Puri / Tim Schulte / Antonio Chaves-Sanjuan / Giulia Mazzini / Serena Caminito / Carlo Pappone / Luigi Anastasia / Paolo Milani / Giampaolo Merlini / Martino Bolognesi / Mario ...Authors: Sarita Puri / Tim Schulte / Antonio Chaves-Sanjuan / Giulia Mazzini / Serena Caminito / Carlo Pappone / Luigi Anastasia / Paolo Milani / Giampaolo Merlini / Martino Bolognesi / Mario Nuvolone / Giovanni Palladini / Stefano Ricagno /
Abstract: Immunoglobulin light chain amyloidosis (AL) is caused by the aberrant production of amyloidogenic light chains (LC) that accumulate as amyloid deposits in vital organs. Distinct LC sequences in each ...Immunoglobulin light chain amyloidosis (AL) is caused by the aberrant production of amyloidogenic light chains (LC) that accumulate as amyloid deposits in vital organs. Distinct LC sequences in each patient yield distinct amyloid structures. However different tissue microenvironments may also cause identical protein precursors to adopt distinct amyloid structures. To address the impact of the tissue environment on the structural polymorphism of amyloids, we extracted fibrils from the kidney of an AL patient (AL55) whose cardiac amyloid structure was previously determined by our group. Here we show that the 4.0 Å resolution cryo-EM structure of the renal fibril is virtually identical to that reported for the cardiac fibril. These results provide the first structural evidence that LC amyloids independently deposited in different organs of the same AL patient share a common fold.
History
DepositionMar 2, 2023-
Header (metadata) releaseAug 16, 2023-
Map releaseAug 16, 2023-
UpdateAug 16, 2023-
Current statusAug 16, 2023Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_16780.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.12 Å/pix.
x 256 pix.
= 285.916 Å
1.12 Å/pix.
x 256 pix.
= 285.916 Å
1.12 Å/pix.
x 256 pix.
= 285.916 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.11686 Å
Density
Contour LevelBy AUTHOR: 0.022
Minimum - Maximum-0.026408736 - 0.064961754
Average (Standard dev.)0.00011840141 (±0.0015359601)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 285.91617 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_16780_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #1

Fileemd_16780_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : Renal AL55 amyloid fibrils

EntireName: Renal AL55 amyloid fibrils
Components
  • Complex: Renal AL55 amyloid fibrils
    • Protein or peptide: Immunoglobulin lambda light chain

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Supramolecule #1: Renal AL55 amyloid fibrils

SupramoleculeName: Renal AL55 amyloid fibrils / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Details: Light chain amyloid fibrils named AL55 extracted from the kidney of an AL amyloidosis patient
Source (natural)Organism: Homo sapiens (human) / Organ: Kidney

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Macromolecule #1: Immunoglobulin lambda light chain

MacromoleculeName: Immunoglobulin lambda light chain / type: protein_or_peptide / ID: 1 / Number of copies: 5 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human) / Organ: Kidney
Molecular weightTheoretical: 23.326557 KDa
SequenceString: NFMLTQPHSV SESPGKTLTI SCTGSSASIA SHYVQWYQQR PGGAPTTLIY ENDQRPSEVP DRFSGSIDSS SNSASLTISG LKTEDEADY YCQSYDGNNH WVFGGGTKLT VLSQPKAAPS VTLFPPSSEE LQANKATLVC LISDFYPGAV TVAWKADSSP V KAGVETTT ...String:
NFMLTQPHSV SESPGKTLTI SCTGSSASIA SHYVQWYQQR PGGAPTTLIY ENDQRPSEVP DRFSGSIDSS SNSASLTISG LKTEDEADY YCQSYDGNNH WVFGGGTKLT VLSQPKAAPS VTLFPPSSEE LQANKATLVC LISDFYPGAV TVAWKADSSP V KAGVETTT PSKQSNNKYA ASSYLSLTPE QWKSHKSYSC QVTHEGSTVE KTVAPTECS

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Experimental details

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Structure determination

Methodcryo EM
Processinghelical reconstruction
Aggregation statefilament

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Sample preparation

BufferpH: 7
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K

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Electron microscopy

MicroscopeFEI TALOS ARCTICA
Image recordingFilm or detector model: FEI FALCON III (4k x 4k) / Number real images: 1819 / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.8 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company

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Image processing

Final reconstructionApplied symmetry - Helical parameters - Δz: 4.9 Å
Applied symmetry - Helical parameters - Δ&Phi: -1.63 °
Applied symmetry - Helical parameters - Axial symmetry: C1 (asymmetric)
Resolution.type: BY AUTHOR / Resolution: 4.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.1) / Number images used: 49091
Segment selectionNumber selected: 98829 / Software - Name: RELION (ver. 3.1)
Startup modelType of model: NONE
Final angle assignmentType: NOT APPLICABLE
FSC plot (resolution estimation)

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Atomic model buiding 1

Initial modelPDB ID:

Chain - Source name: PDB / Chain - Initial model type: experimental model
RefinementSpace: REAL
Output model

PDB-8cpe:
CryoEM structure of AL55 amyloid fibrils extracted from the kidney of an AL amyloidosis patient.

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