9wl7

ALECT2 type IIa filament from renal biopsy tissue of an individual with ALECT2 amyloidosis

spinqualitylabelsall models 9wl7, resolution 2.93Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9wl7 is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.93Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function LECT2_HUMAN Has a neutrophil chemotactic activity. Also a positive regulator of chondrocyte proliferation. Publication Abstract from PubMed Leukocyte chemotactic factor 2 is a recently identified amyloidogenic protein, whose abnormal aggregation defines a systemic amyloidosis termed ALECT2 amyloidosis. Due to the lack of reliable biomarkers, diagnosis relies primarily on histological demonstration and typing of amyloid deposits in renal biopsies. However, immunohistochemical detection of ALECT2 is often inconsistent, leading to diagnostic uncertainty. The underlying basis remains poorly understood, reflecting our limited knowledge of ALECT2 deposits. Here, using cryo-electron microscopy (cryo-EM), we determined the structures of ALECT2 filaments from renal biopsies of five living patients. Unlike filaments assembled from recombinant proteins in vitro, all 133 residues of mature LECT2 are incorporated into the filament cores, with native disulfide linkages preserved. The filaments consistently adopt the shared six-layered folds in all five patients, indicating a common mechanism of amyloidogenesis. Because all residues are incorporated into the fibril core, epitope accessibility is limited. This can explain variability in immunohistochemical detection and thus highlights the need for conformation-specific antibodies and antibody-independent detection strategies for improving diagnostic accuracy. This biopsy-based workflow not only expands the availability of patient-derived tissue for cryo-EM studies but also demonstrates the potential of cryo-EM as a tool for precise diagnosis of systemic amyloidosis. Cryo-EM structures of ALECT2 filaments from human renal biopsies.,Zheng JL, Zheng YX, Chen K, Wang S, Liang JW, Wang SX, Yang L, Shi Y Nat Commun. 2026 May 22. doi: 10.1038/s41467-026-73602-2. PMID:42173881 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA