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Cryo-EM structure of a lysozyme-derived amyloid fibril from hereditary amyloidosis

ABSTRACT: Systemic ALys amyloidosis is a debilitating protein misfolding diseases that arises from the formation of amyloid fibrils from C-type lysozyme. We here present a 2.8 A cryo-electron microscopy structure of an amyloid fibril, which was isolated from the abdominal fat tissue of a patient who expressed the D87G variant of human lysozyme. We find that the fibril possesses a stable core that is formed by all 130 residues of the fibril precursor protein. There are four disulfide bonds in each fibril protein that connect the same residues as in the globularly folded protein. However, the conformation is fundamentally different in the fibril and in native lysozyme, demonstrating the need of protein unfolding. The position of the mutant residue within the fibril structure implies that the role of this mutation includes the stabilization of the pathogenic fibril structure.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Marcus Faendrich

PROVIDER: MSV000096142 | MassIVE | Mon Oct 21 06:31:00 BST 2024

SECONDARY ACCESSION(S): PXD057013

REPOSITORIES: MassIVE

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Cryo-EM structure of a lysozyme-derived amyloid fibril from hereditary amyloidosis

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