9OKA

Cardiac lambda-6 light chain amyloid AL-224L single protofilament

Summary for 9OKA

• Entry DOI: 10.2210/pdb9oka/pdb
• EMDB information: 70557
• Descriptor: Immunoglobulin l6 light-chain AL-224L (1 entity in total)
• Functional Keywords: amyloid, heart, immunoglobulin, light-chain, protein fibril
• Biological source: Homo sapiens
• Total number of polymer chains: 5
• Total formula weight: 62337.38

Authors

Hicks, C.W.,Gursky, O.,Huda, N. (deposition date: 2025-05-09, release date: 2025-12-24, Last modification date: 2026-01-07)

Primary citation

Hicks, C.W.,Prokaeva, T.,Spencer, B.,Jayaraman, S.,Huda, N.,Wong, S.,Chen, H.,Sanchorawala, V.,Lavatelli, F.,Gursky, O.
Cryo-EM of Cardiac AL-224L Amyloid Reveals Shared Structural Motifs and Mutation-induced Differences in lambda 6 Light Chain Fibrils.
J.Mol.Biol., 438:169591-169591, 2025

PubMed Abstract: 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.

PubMed: 41389958
DOI: 10.1016/j.jmb.2025.169591

Experimental method

ELECTRON MICROSCOPY (2.92 Å)