ArticleBiochemistry2019
Mechanistic Insights into the Early Events in the Aggregation of Immunoglobulin Light Chains.
Article in Biochemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- The Heart of the Alzheimer's: A Mindful View of Heart Disease.Frontiers in physiology · 2020Pooled it
- Sequential cryoglobulinemia-associated glomerulonephritis and light-chain amyloidosis in monoclonal gammopathy of renal significance.CEN case reports · 2026Article
- Article
- Clone-specific residue changes at multiple positions are associated with amyloid formation by antibody light chains.Frontiers in immunology · 2025Article
- Protein Misfolding and Aggregation of Pathological IgG Light Chains in Oncohematological Dyscrasias: From Molecular Pathways to Clinical Implications.Current protein & peptide science · 2025Review
- Amyloids and the Heart: An Update.Journal of clinical medicine · 2024Review
- Amyloidosis in Childhood: A Review of Clinical Features and Comparison with Adult Forms.Journal of clinical medicine · 2024Review
- 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
- A thermodynamic investigation into protein-excipient interactions involving different grades of polysorbate 20 and 80.Journal of thermal analysis and calorimetry · 2024Article
- Mechanistic insights into the aggregation pathway of the patient-derived immunoglobulin light chain variable domain protein FOR005.Nature communications · 2023Article
- Noninvasive Diagnostics of Renal Amyloidosis: Current State and Perspectives.International journal of molecular sciences · 2022Review
- Molecular Mechanism of Pathogenesis and Treatment Strategies for AL Amyloidosis.International journal of molecular sciences · 2022Review
- Amyloidosis: What does pathology offer? The evolving field of tissue biopsy.Frontiers in cardiovascular medicine · 2022Review
- Silver Nanoparticles as a Tool for the Study of Spontaneous Aggregation of Immunoglobulin Monoclonal Free Light Chains.International journal of molecular sciences · 2021Article
- Early events in light chain aggregation at physiological pH reveal new insights on assembly, stability, and aggregate dissociation.Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis · 2021Article
- Pathophysiology and Therapeutic Approaches to Cardiac Amyloidosis.Circulation research · 2021Review
- Future Perspectives.Hematology/oncology clinics of North America · 2020Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Little is known about the mechanism of amyloid assembly in immunoglobulin light chain (AL) amyloidosis, in contrast to other amyloid diseases. Early events in the aggregation pathway are especially important, as these soluble species could be cytotoxic intermediates playing a critical role in the initiation of the amyloid assembly. In this work, we discuss the mechanism of the early events in in vitro fibril formation of immunoglobulin light chain AL-09 and AL-12 (involved in cardiac amyloidosis) and its germline (control) protein κI O18/O8. Previous work from our laboratory showed that AL-12 adopts a canonical dimer conformation (like the germline protein), whereas AL-09 presents an altered dimer interface as a result of somatic mutations. Both AL-12 and AL-09 aggregate with similar rates and significantly faster than the germline protein. AL-09 is the only protein in this study that forms stable oligomeric intermediates during the early stages of the aggregation reaction with some structural rearrangements that increase the thioflavin T fluorescence but maintain the same number of monomers in solution. The presence of the restorative mutation AL-09 H87Y changes the kinetics and the aggregation pathway compared to AL-09. The single restorative mutation AL-12 R65S slightly delayed the overall rate of aggregation as compared to AL-12. Collectively, our study provides a comprehensive analysis of species formed during amyloid nucleation in AL amyloidosis, shows a strong dependence between the altered dimer conformation and the formation of stable oligomeric intermediates, and sheds light on the structural features of amyloidogenic intermediates associated with cellular toxicity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.