{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Hicks CW"],"funding":["NIGMS NIH HHS","NIH HHS"],"pubmed_abstract":["In amyloid light chain (AL) amyloidosis, 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 amyloidosis. Comparison with λ6-LC structures from two other patients reveals similarities in amyloid folds. Mutation-induced structural differences in AL-224L include altered C-terminal conformation with an exposed ligand-binding surface; 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 suggest shared features in λ6-LC amyloid folds and reveal how mutation-induced structural changes influence amyloid-ligand interactions in a patient-specific manner."],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2025.06.25.661559"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12236830"],"repository":["biostudies-literature"],"pubmed_title":["Cryo-EM of cardiac AL-224L amyloid reveals shared features in λ6 light chain fibril folds."],"pmcid":["PMC12236830"],"funding_grant_id":["S10 OD032253","R01 GM135158","R01 GM067260"],"pubmed_authors":["Hicks CW","Wong S","Huda N","Prokaeva T","Gursky O","Lavatelli F","Jayaraman S","Chen H","Spencer B","Sanchorawala V"],"additional_accession":[]},"is_claimable":false,"name":"Cryo-EM of cardiac AL-224L amyloid reveals shared features in λ6 light chain fibril folds.","description":"In amyloid light chain (AL) amyloidosis, 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 amyloidosis. Comparison with λ6-LC structures from two other patients reveals similarities in amyloid folds. Mutation-induced structural differences in AL-224L include altered C-terminal conformation with an exposed ligand-binding surface; 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 suggest shared features in λ6-LC amyloid folds and reveal how mutation-induced structural changes influence amyloid-ligand interactions in a patient-specific manner.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jul","modification":"2025-08-23T03:09:19.317Z","creation":"2025-08-23T03:09:19.317Z"},"accession":"S-EPMC12236830","cross_references":{"pubmed":["40631131"],"doi":["10.1101/2025.06.25.661559"]}}