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-Structure paper
Title | Role of mutations and post-translational modifications in systemic AL amyloidosis studied by cryo-EM. |
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Journal, issue, pages | Nat Commun, Vol. 12, Issue 1, Page 6434, Year 2021 |
Publish date | Nov 5, 2021 |
Authors | Lynn Radamaker / Sara Karimi-Farsijani / Giada Andreotti / Julian Baur / Matthias Neumann / Sarah Schreiner / Natalie Berghaus / Raoul Motika / Christian Haupt / Paul Walther / Volker Schmidt / Stefanie Huhn / Ute Hegenbart / Stefan O Schönland / Sebastian Wiese / Clarissa Read / Matthias Schmidt / Marcus Fändrich / |
PubMed Abstract | 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 ...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 λ1-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. |
External links | Nat Commun / PubMed:34741031 / PubMed Central |
Methods | EM (helical sym.) |
Resolution | 3.1 Å |
Structure data | EMDB-12570, PDB-7nsl: |
Source |
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Keywords | IMMUNE SYSTEM / amyloid / antibody / systemic amyloidosis / light chain |