The AL Amyloid Fibril: Looking for a Link between Fibril Formation and Structure
Christian Haupt
- Vol. 2, Iss: 3, pp 505-514
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TLDR
Recent biochemical and biophysical studies that have expanded knowledge on how versatile the structure of AL fibrils in patients is are reviewed and highlighted their implications for the molecular mechanism of fibril formation in AL amyloidosis are highlighted.Abstract:
The formation and deposition of fibrils derived from immunglobulin light chains is a hallmark of systemic AL amyloidosis. A particularly remarkable feature of the disease is the diversity and complexity in pathophysiology and clinical manifestations. This is related to the variability of immunoglobulins, as virtually every patient has a variety of mutations resulting in their own unique AL protein and thus a unique fibril deposited in the body. Here, I review recent biochemical and biophysical studies that have expanded our knowledge on how versatile the structure of AL fibrils in patients is and highlight their implications for the molecular mechanism of fibril formation in AL amyloidosis.read more
Citations
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Transient disorder along pathways to amyloid
TL;DR: In this article, high-resolution structures of amyloid fibrils formed from normally-folded proteins have revealed non-native conformations of the polypeptide chains, in contrast to earlier models that posited a role for assembly of partially folded proteins.
Journal ArticleDOI
Concurrent light chain amyloidosis and proximal tubulopathy: Insights into different aggregation behavior—A case report
Simone Feurstein,Julian Zoller,Constantin Schwab,S. Schreiner,Heiko M. Mundt,Iris Breitkreutz,Brigitte Schneider,Jörg Beimler,Martin Zeier,Rüdiger Waldherr,Stefan Gröschel,Carsten Müller-Tidow,Stefan Schönland,Ute Hegenbart +13 more
TL;DR: In this paper , the first case of concurrent AL amyloidosis and a subclass of MGRS, light chain proximal tubulopathy (LCPT), was reported in a 53-year-old female with smoldering myeloma immunoglobulin G kappa.
References
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Journal ArticleDOI
Immunoglobulin light chain amyloid aggregation
Luis M. Blancas-Mejia,Pinaki Misra,Christopher J. Dick,Shawna A. Cooper,Keely R. Redhage,Michael R. Bergman,Torri L. Jordan,Khansaa Maar,Marina Ramirez-Alvarado +8 more
TL;DR: The factors that contribute to AL amyloidosis complexity are reviewed, the findings by the laboratory from the last 16 years and the work from other laboratories on understanding the structural, kinetics, and thermodynamic contributions that drive immunoglobulin light chain-associated amyloidsosis are reviewed.
Journal ArticleDOI
Immunoglobulin Light Chain Gene Rearrangements, Receptor Editing and the Development of a Self-Tolerant Antibody Repertoire.
TL;DR: This review explores germline and rearranged light chain genes in a variety of species, with a particular focus on human and mouse genes, and considers how primary rearrangements and receptor editing together shape the expressed light chain repertoire.
Journal ArticleDOI
Fibril protein fragmentation pattern in systemic AL-amyloidosis.
TL;DR: The results strongly support the hypothesis that proteolytic cleavage occurs after fibril formation in amyloid of different organs in one patient but differed greatly between patients.
Journal ArticleDOI
Identification and Location of a Cysteinyl Posttranslational Modification in an Amyloidogenic κ1 Light Chain Protein by Electrospray Ionization and Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry
TL;DR: The methods used in this report enable high-sensitivity determination of amino acid sequence and variation in intact and truncated light chains as well as posttranslational modifications.
Journal ArticleDOI
Cryo-EM reveals structural breaks in a patient-derived amyloid fibril from systemic AL amyloidosis
Lynn Radamaker,Julian David Baur,Stefanie Huhn,Christian Haupt,Ute Hegenbart,Stefan Schönland,Akanksha Bansal,Matthias Schmidt,Marcus Fändrich +8 more
TL;DR: In this paper, the authors presented two ex vivo fibril structures of a λ3 LC-derived amyloid fibrils that were extracted from the explanted heart of a patient (FOR005).