ArticleThe FEBS journal2022
Protease-sensitive regions in amyloid light chains: what a common pattern of fragmentation across organs suggests about aggregation.
Article in The FEBS journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 43 citations in OpenAlex.
- Small Molecule Stabilization of Diverse Amyloidogenic Immunoglobulin Light Chains Revealed by Hydrogen-Deuterium Exchange Mass Spectrometry.Journal of molecular biology · 2026Article
- Mass Spectrometry-Based De Novo Sequencing of N-Glycosylated Light Chains: Linking Urinary Proteoforms to In Situ Renal Amyloid Deposits.Molecular & cellular proteomics : MCP · 2026Article
- Beyond Sequence: Posttranslational Remodeling of Antigens in Autoimmunity.Immunological reviews · 2026Review
- Small molecule stabilization of diverse amyloidogenic immunoglobulin light chains revealed by hydrogen-deuterium exchange mass spectrometry.bioRxiv : the preprint server for biology · 2026Article
- Article
- Conformational Differences in the Light Chain Constant Domain of Immunoglobulin G and Free Light Chain May Influence Proteolysis in AL Amyloidosis.Journal of molecular biology · 2024Article
- Predicting Structural Consequences of Antibody Light Chain N-Glycosylation in AL Amyloidosis.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Helical superstructures between amyloid and collagen in cardiac fibrils from a patient with AL amyloidosis.Nature communications · 2024Article
- Biophysical characterization of human-cell-expressed, full-length κI O18/O8, AL-09, λ6a, and Wil immunoglobulin light chains.Biochimica et biophysica acta. Proteins and proteomics · 2024Article
- Kinetic evidence for multiple aggregation pathways in antibody light chain variable domains.Protein science : a publication of the Protein Society · 2024Article
- Role of complementarity-determining regions 1 and 3 in pathologic amyloid formation by human immunoglobulin κ1 light chains.Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis · 2023Article
- Common transthyretin-derived amyloid fibril structures in patients with hereditary ATTR amyloidosis.Nature communications · 2023Article
- Diagnostic Challenges and Solutions in Systemic Amyloidosis.International journal of molecular sciences · 2023Review
- Complete variable domain sequences of monoclonal antibody light chains identified from untargeted RNA sequencing data.Frontiers in immunology · 2023Article
- Cu(II) Binding Increases the Soluble Toxicity of Amyloidogenic Light Chains.International journal of molecular sciences · 2022Article
- Understanding AL amyloidosis with a little help fromFrontiers in immunology · 2022Review
- Dynamic protein structures in normal function and pathologic misfolding in systemic amyloidosis.Biophysical chemistry · 2022Review
- A Conservative Point Mutation in a Dynamic Antigen-binding Loop of Human Immunoglobulin λ6 Light Chain Promotes Pathologic Amyloid Formation.Journal of molecular biology · 2021Article
- Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Light-chain (AL) amyloidosis is characterized by deposition of immunoglobulin light chains (LC) as fibrils in target organs. Alongside the full-length protein, abundant LC fragments are always present in AL deposits. Herein, by combining gel-based and mass spectrometry analyses, we identified and compared the fragmentation sites of amyloid LCs from multiple organs of an AL λ amyloidosis patient (AL-55). The positions pinpointed here in kidney and subcutaneous fat, alongside those previously detected in heart of the same patient, were aligned and mapped on the LC's dimeric and fibrillar states. All tissues contain fragmented LCs along with the full-length protein; the fragment pattern is coincident across organs, although microheterogeneity exists. Multiple cleavage positions were detected; some are shared, whereas some are organ-specific, likely due to a complex of proteases. Cleavage sites are concentrated in 'proteolysis-prone' regions, common to all tissues. Several proteolytic sites are not accessible on native dimers, while they are compatible with fibrils. Overall, data suggest that the heterogeneous ensemble of LC fragments originates in tissues and is consistent with digestion of preformed fibrils, or with the hypothesis that initial proteolytic cleavage of the constant domain triggers the amyloidogenic potential of LCs, followed by subsequent proteolytic degradation. This work provides a unique set of molecular data on proteolysis from ex vivo amyloid, which allows discussing hypotheses on role and timing of proteolytic events occurring along amyloid formation and accumulation in AL patients.
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