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Yorodumi- EMDB-49623: Cryo-EM structure of amyloid fibril isolated from the kidney of a... -
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Basic information
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| Title | Cryo-EM structure of amyloid fibril isolated from the kidney of a variant ALECT2-I40V amyloidosis patient | ||||||||||||
Map data | combined map from two halfmaps | ||||||||||||
Sample |
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Keywords | Leukocyte cell-derived chemotaxin-2 / LECT2 / systemic amyloidosis / ALECT2 / systemic / amyloid / kidney. / PROTEIN FIBRIL | ||||||||||||
| Biological species | Homo sapiens (human) | ||||||||||||
| Method | helical reconstruction / cryo EM / Resolution: 5.6 Å | ||||||||||||
Authors | Nguyen B / Saelices L | ||||||||||||
| Funding support | United States, 3 items
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Citation | Journal: Nat Commun / Year: 2026Title: 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 |
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_49623.map.gz | 139.5 MB | EMDB map data format | |
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| Header (meta data) | emd-49623-v30.xml emd-49623.xml | 18 KB 18 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_49623_fsc.xml | 16.5 KB | Display | FSC data file |
| Images | emd_49623.png | 65.3 KB | ||
| Filedesc metadata | emd-49623.cif.gz | 5.3 KB | ||
| Others | emd_49623_half_map_1.map.gz emd_49623_half_map_2.map.gz | 140.6 MB 140.3 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-49623 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-49623 | HTTPS FTP |
-Related structure data
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Map
| File | Download / File: emd_49623.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Annotation | combined map from two halfmaps | ||||||||||||||||||||||||||||||||||||
| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.954 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Half map: halfmap1
| File | emd_49623_half_map_1.map | ||||||||||||
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| Annotation | halfmap1 | ||||||||||||
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| Density Histograms |
-Half map: halfmap2
| File | emd_49623_half_map_2.map | ||||||||||||
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| Annotation | halfmap2 | ||||||||||||
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| Density Histograms |
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Sample components
-Entire : Leukocyte cell-derived chemotaxin-2 protein
| Entire | Name: Leukocyte cell-derived chemotaxin-2 protein |
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| Components |
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-Supramolecule #1: Leukocyte cell-derived chemotaxin-2 protein
| Supramolecule | Name: Leukocyte cell-derived chemotaxin-2 protein / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all Details: fibrillation of Leukocyte cell-derived chemotaxin-2 protein |
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| Source (natural) | Organism: Homo sapiens (human) / Organ: Kidney / Tissue: Kidney |
-Macromolecule #1: Leukocyte cell-derived chemotaxin-2
| Macromolecule | Name: Leukocyte cell-derived chemotaxin-2 / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) / Organ: Kidney / Tissue: Kidney |
| Sequence | String: 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 |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | helical reconstruction |
| Aggregation state | filament |
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Sample preparation
| Buffer | pH: 7 / Details: extracted in water |
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| Grid | Model: 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 |
| Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 298 K |
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Electron microscopy
| Microscope | TFS KRIOS |
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| Image recording | Film 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 beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | Illumination 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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About Yorodumi



Keywords
Homo sapiens (human)
Authors
United States, 3 items
Citation



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Processing
FIELD EMISSION GUN

