Cryo-EM Structure of a Human LECT2 Amyloid Fibril Reveals a Network of Polar Ladders at its Core.

ABSTRACT: ALECT2 is a type of systemic amyloidosis caused by deposition of the leukocyte cell-derived chemotaxin-2 (LECT2) protein in the form of fibrils. In ALECT2, LECT2 fibril deposits can be found in the glomerulus, resulting in renal failure. Affected patients lack effective treatment options outside of renal transplant or dialysis. While the structure of LECT2 in its globular form has been determined by X-ray crystallography, structures of LECT2 amyloid fibrils remain unknown. Using single particle cryo-EM, we now find that human LECT2 forms robust twisting fibrils with canonical amyloid features. At their core, LECT2 fibrils contain two mating protofilaments, the ordered core of each protofilament spans residues 55-75 of the LECT2 sequence. The overall geometry of the LECT2 fibril displays fe

SUBMITTER: Richards LS 

PROVIDER: S-EPMC9934627 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature