Role of mutations and post-translational modifications in systemic AL amyloidosis studied by cryo-EM
| العنوان: | Role of mutations and post-translational modifications in systemic AL amyloidosis studied by cryo-EM |
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| المؤلفون: | Sara Karimi-Farsijani, Stefanie Huhn, Marcus Fändrich, Lynn Radamaker, Julian David Baur, Giada Andreotti, Paul Walther, Matthias Neumann, Sarah Schreiner, Volker Schmidt, Clarissa Read, Matthias Schmidt, Ute Hegenbart, Christian Haupt, Stefan Schönland, Raoul Motika, Sebastian Wiese, Natalie Berghaus |
| المصدر: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-11 (2021) |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | INVOLVEMENT, Protein Folding, Glycosylation, PREDICTION, Protein Conformation, General Physics and Astronomy, Protein aggregation, Aggregation (Chemistry), Immunoglobulin light-chain amyloidosis, chemistry.chemical_compound, DDC 570 / Life sciences, FIBRILS, Cryoelectron microscopy, Immunoglobulin Light-chain Amyloidosis, Multidisciplinary, Strukturbiologie, Immunglobuline, lipids (amino acids, peptides, and proteins), Structural biology, GERMLINE GENE, Amyloid, Science, Somatic hypermutation, Immunoglobulins, macromolecular substances, Fibril, Immunoglobulin light chain, DEPOSITS, General Biochemistry, Genetics and Molecular Biology, Article, ddc:570, AL amyloidosis, medicine, ddc:610, LAMBDA-III, Immunoglobulin light chains, General Chemistry, Amyloidose, medicine.disease, carbohydrates (lipids), chemistry, Mutation, Biophysics, VISUALIZATION, Cryoelectron tomography, DDC 610 / Medicine & health |
| الوصف: | Systemic AL amyloidosis is a rare disease that is caused by the misfolding of immunoglobulin light chains (LCs). Potential drivers of amyloid formation in this disease are post-translational modifications (PTMs) and the mutational changes that are inserted into the LCs by somatic hypermutation. Here we present the cryo electron microscopy (cryo-EM) structure of an ex vivo ��1-AL amyloid fibril whose deposits disrupt the ordered cardiomyocyte structure in the heart. The fibril protein contains six mutational changes compared to the germ line and three PTMs (disulfide bond, N-glycosylation and pyroglutamylation). Our data imply that the disulfide bond, glycosylation and mutational changes contribute to determining the fibril protein fold and help to generate a fibril morphology that is able to withstand proteolytic degradation inside the body. publishedVersion |
| وصف الملف: | application/pdf |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ebd3e500479b0af12a5673f1585a4e06Test https://pubmed.ncbi.nlm.nih.gov/34741031Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ebd3e500479b0af12a5673f1585a4e06 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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