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TitleCryo-EM of Cardiac AL-224L Amyloid Reveals Shared Structural Motifs and Mutation-induced Differences in λ6 Light Chain Fibrils.
Journal, issue, pagesJ Mol Biol, Vol. 438, Issue 3, Page 169591, Year 2026
Publish dateDec 11, 2025
AuthorsChad W Hicks / Tatiana Prokaeva / Brian Spencer / Shobini Jayaraman / Noorul Huda / Sherry Wong / Hui Chen / Vaishali Sanchorawala / Francesca Lavatelli / Olga Gursky /
PubMed AbstractIn light chain amyloidosis (AL), aberrant monoclonal antibody light chains (LCs) deposit in vital organs causing organ damage. Each AL patient features a unique LC; previous cryogenic electron ...In light chain amyloidosis (AL), aberrant monoclonal antibody light chains (LCs) deposit in vital organs causing organ damage. Each AL patient features a unique LC; previous cryogenic electron microscopy (cryo-EM) studies revealed different amyloid structures in different AL patients. How LC mutations influence amyloid structures remains unclear. We report a cryo-EM structure of cardiac AL-224L amyloid (2.92 Å resolution) from λ6-LC family, which is overrepresented in AL amyloidosis. Comparison with λ6-LC structures from two other patients reveals similarities in amyloid folds, along with major differences caused by specific mutations. Differences in AL-224L include altered C-terminal conformation with an exposed surface forming an apparent ligand-binding site; an enlarged hydrophilic pore with orphan density; and altered steric zipper registry with backbone flipping, which likely represent general adaptive mechanisms in amyloids. The results reveal shared features in λ6-LC amyloid folds and suggest how mutation-induced structural changes influence amyloid-ligand interactions in a patient-specific manner.
External linksJ Mol Biol / PubMed:41389958 / PubMed Central
MethodsEM (helical sym.)
Resolution2.92 Å
Structure data

70557

9oka

EMDB-70557, PDB-9oka:
Cardiac lambda-6 light chain amyloid AL-224L single protofilament
Method: EM (helical sym.) / Resolution: 2.92 Å

Source
  • homo sapiens (human)
KeywordsPROTEIN FIBRIL / amyloid / heart / immunoglobulin / light-chain

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