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- EMDB-49623: Cryo-EM structure of amyloid fibril isolated from the kidney of a... -

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Entry
Database: EMDB / ID: EMD-49623
TitleCryo-EM structure of amyloid fibril isolated from the kidney of a variant ALECT2-I40V amyloidosis patient
Map datacombined map from two halfmaps
Sample
  • Complex: Leukocyte cell-derived chemotaxin-2 protein
    • Protein or peptide: Leukocyte cell-derived chemotaxin-2
KeywordsLeukocyte cell-derived chemotaxin-2 / LECT2 / systemic amyloidosis / ALECT2 / systemic / amyloid / kidney. / PROTEIN FIBRIL
Biological speciesHomo sapiens (human)
Methodhelical reconstruction / cryo EM / Resolution: 5.6 Å
AuthorsNguyen B / Saelices L
Funding support United States, 3 items
OrganizationGrant numberCountry
American Heart Association847236 United States
National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)DP2-HL163810 United States
Welch FoundationI-2121-20220331 United States
CitationJournal: Nat Commun / Year: 2026
Title: Structural polymorphism of ex-vivo ALECT2 amyloid fibrils revealed by cryo-EM.
Authors: Shumaila Afrin / Binh An Nguyen / Virender Singh / Preeti Singh / Parker Bassett / Maja Pekala / Bret Evers / Christian Lopez / Yasmin Ahmed / Li Li / Raja Reddy Kallem / Andrew Lemoff / ...Authors: Shumaila Afrin / Binh An Nguyen / Virender Singh / Preeti Singh / Parker Bassett / Maja Pekala / Bret Evers / Christian Lopez / Yasmin Ahmed / Li Li / Raja Reddy Kallem / Andrew Lemoff / Christos Argyropoulos / Barbara Kluve-Beckerman / Lorena Saelices /
Abstract: ALECT2 amyloidosis is a rare systemic disease characterized by the pathological deposition of leukocyte cell-derived chemotaxin-2 (LECT2) as amyloid fibrils, primarily affecting the kidneys and liver. ...ALECT2 amyloidosis is a rare systemic disease characterized by the pathological deposition of leukocyte cell-derived chemotaxin-2 (LECT2) as amyloid fibrils, primarily affecting the kidneys and liver. The molecular mechanisms underlying LECT2 aggregation remain poorly defined, hindering diagnostic and therapeutic development. Here, we present cryo-electron microscopy structures of ex-vivo ALECT2 fibrils extracted from a patient's kidney. We identified three fibril polymorphs: a predominant single-protofilament morphology and two minor double-protofilament morphologies. The dominant single-protofilament morphology comprises the full-length 133-residue LECT2 protein and retains all three native disulfide bonds. Low-resolution reconstructions of double-protofilament morphologies suggest they adopt a similar fold to the single protofilament morphology, but form paired assemblies with different inter-filament interfaces. Mass spectrometry also reveals acetylation within the fibrils. These findings offer critical insights into the structural basis of ALECT2 amyloid formation and identify molecular features that could inform future diagnostic and therapeutic approaches.
History
DepositionMar 10, 2025-
Header (metadata) releaseFeb 11, 2026-
Map releaseFeb 11, 2026-
UpdateApr 29, 2026-
Current statusApr 29, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_49623.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationcombined map from two halfmaps
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.95 Å/pix.
x 360 pix.
= 343.44 Å
0.95 Å/pix.
x 360 pix.
= 343.44 Å
0.95 Å/pix.
x 360 pix.
= 343.44 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.954 Å
Density
Contour LevelBy AUTHOR: 0.015
Minimum - Maximum-0.011290894 - 0.037534297
Average (Standard dev.)0.0008405374 (±0.004384686)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions360360360
Spacing360360360
CellA=B=C: 343.44 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: halfmap1

Fileemd_49623_half_map_1.map
Annotationhalfmap1
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: halfmap2

Fileemd_49623_half_map_2.map
Annotationhalfmap2
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : Leukocyte cell-derived chemotaxin-2 protein

EntireName: Leukocyte cell-derived chemotaxin-2 protein
Components
  • Complex: Leukocyte cell-derived chemotaxin-2 protein
    • Protein or peptide: Leukocyte cell-derived chemotaxin-2

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Supramolecule #1: Leukocyte cell-derived chemotaxin-2 protein

SupramoleculeName: Leukocyte cell-derived chemotaxin-2 protein / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Details: fibrillation of Leukocyte cell-derived chemotaxin-2 protein
Source (natural)Organism: Homo sapiens (human) / Organ: Kidney / Tissue: Kidney

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Macromolecule #1: Leukocyte cell-derived chemotaxin-2

MacromoleculeName: Leukocyte cell-derived chemotaxin-2 / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human) / Organ: Kidney / Tissue: Kidney
SequenceString:
GPWANICAGK SSNEIRTCD R HGCGQYSA QR SQRPHQG VDV LCSAGS TVYA PFTGM IVGQE KPYQ NKNAIN NGV RISGRGF CV KMFYIKPI K YKGPIKKGE KLGTLLPLQK VYPGIQSHV H IENCDSSD PT AYL

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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 / Details: extracted in water
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 30 sec. / Pretreatment - Atmosphere: AIR
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 298 K

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Number grids imaged: 1 / Number real images: 22899 / Average exposure time: 3.69 sec. / Average electron dose: 40.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.6 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Final reconstructionApplied symmetry - Helical parameters - Δz: 4.75 Å
Applied symmetry - Helical parameters - Δ&Phi: -0.8 °
Applied symmetry - Helical parameters - Axial symmetry: C1 (asymmetric)
Resolution.type: BY AUTHOR / Resolution: 5.6 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 4.0) / Number images used: 12405
CTF correctionSoftware - Name: CTFFIND (ver. 4.1) / Type: NONE
Segment selectionNumber selected: 179392 / Software - Name: RELION (ver. 4.0)
Details: We used Relion built-in Topaz to autopick this dataset.
Startup modelType of model: INSILICO MODEL / In silico model: generated using relion_helix_inimodel2d
Final angle assignmentType: NOT APPLICABLE / Software - Name: RELION (ver. 4.0)
FSC plot (resolution estimation)

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