Structural polymorphism of <i>ex-vivo</i> ALECT2 amyloid fibrils revealed by cryo-EM.

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. 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 sugges

SUBMITTER: Afrin S 

PROVIDER: S-EPMC12338731 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature