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TitleStructural polymorphism of ex-vivo ALECT2 amyloid fibrils revealed by cryo-EM.
Journal, issue, pagesNat Commun, Year 2026
Publish dateApr 11, 2026
AuthorsShumaila 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 /
PubMed AbstractALECT2 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.
External linksNat Commun / PubMed:41965342
MethodsEM (helical sym.)
Resolution2.4 - 5.6 Å
Structure data

EMDB-49601, PDB-9non:
Cryo-EM structure of amyloid fibril isolated from the kidney of a variant Alect2-I40V amyloidosis patient
Method: EM (helical sym.) / Resolution: 2.4 Å

EMDB-49623: Cryo-EM structure of amyloid fibril isolated from the kidney of a variant ALECT2-I40V amyloidosis patient
Method: EM (helical sym.) / Resolution: 5.6 Å

EMDB-49624: Cryo-EM structure of amyloid fibril isolated from the kidney of a variant ALECT2-I40V amyloidosis patient
Method: EM (helical sym.) / Resolution: 5.0 Å

Source
  • homo sapiens (human)
KeywordsPROTEIN FIBRIL / Leukocyte cell-derived chemotaxin-2 / LECT2 / systemic amyloidosis / ALECT2 / systemic / amyloid / kidney.

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