Cryo-EM reveals structural breaks in a patient-derived amyloid fibril from systemic AL amyloidosis
| العنوان: | Cryo-EM reveals structural breaks in a patient-derived amyloid fibril from systemic AL amyloidosis |
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| المؤلفون: | Stefan Schönland, Matthias Schmidt, Akanksha Bansal, Ute Hegenbart, Marcus Fändrich, Christian Haupt, Julian David Baur, Lynn Radamaker, Stefanie Huhn |
| المصدر: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-10 (2021) |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Amyloid, Cryo-electron microscopy, Protein Conformation, Science, Sequence (biology), macromolecular substances, Immunoglobulin light chain, Fibril, Article, Protein Aggregates, Variable domain, AL amyloidosis, medicine, Humans, Immunoglobulin Light-chain Amyloidosis, Amino Acid Sequence, Chemistry, Cryoelectron Microscopy, Middle Aged, Amyloid fibril, medicine.disease, Mutation, Biophysics, Fatal disease, Female, Immunoglobulin Light Chains, Protein aggregation, Structural biology |
| الوصف: | Systemic AL amyloidosis is a debilitating and potentially fatal disease that arises from the misfolding and fibrillation of immunoglobulin light chains (LCs). The disease is patient-specific with essentially each patient possessing a unique LC sequence. In this study, we present two ex vivo fibril structures of a λ3 LC. The fibrils were extracted from the explanted heart of a patient (FOR005) and consist of 115-residue fibril proteins, mainly from the LC variable domain. The fibril structures imply that a 180° rotation around the disulfide bond and a major unfolding step are necessary for fibrils to form. The two fibril structures show highly similar fibril protein folds, differing in only a 12-residue segment. Remarkably, the two structures do not represent separate fibril morphologies, as they can co-exist at different z-axial positions within the same fibril. Our data imply the presence of structural breaks at the interface of the two structural forms. Systemic AL amyloidosis is a protein misfolding disease caused by the aggregation and fibrillation of immunoglobulin light chains (LCs). Here, the authors present the cryo-EM structures of λ3 LC-derived amyloid fibrils that were isolated from patient tissue and they observe structural breaks, where the two different fibril structures co-exist at different z-axial positions within the same fibril. |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f3e1bec955e12e28b5adc33371c1b5abTest https://pubmed.ncbi.nlm.nih.gov/33558536Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f3e1bec955e12e28b5adc33371c1b5ab |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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