Role of mutations and post-translational modifications in systemic AL amyloidosis studied by cryo-EM

@article{Radamaker2021RoleOM,
  title={Role of mutations and post-translational modifications in systemic AL amyloidosis studied by cryo-EM},
  author={Lynn Radamaker and Sara Karimi-Farsijani and Giada Andreotti and Julian Baur and Matthias Neumann and Sarah Schreiner and Natalie Berghaus and Raoul Motika and Christian Haupt and Paul Walther and Volker Schmidt and Stefanie Huhn and Ute Hegenbart and Stefan O. Sch{\"o}nland and Sebastian Wiese and Clarissa Read and Matthias Schmidt and Marcus F{\"a}ndrich},
  journal={Nature Communications},
  year={2021},
  volume={12}
}
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… 

Identification of AL proteins from 10 λ-AL amyloidosis patients by mass spectrometry extracted from abdominal fat and heart tissue.

  • Julian BaurNatalie Berghaus Christian Haupt
  • Biology
    Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
  • 2022
TLDR
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Insight is provided into how SOD1 converts between structurally and functionally distinct states by producing cytotoxic amyloid fibrils from full-length apo human S OD1 under reducing conditions and determining the atomic structure using cryo-EM.

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TLDR
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TLDR
This review addresses what the authors currently know about why and how certain light chains are prone to forming amyloid and analyzes the structural bases of this type of aggregate, including the origin of its structural diversity.

Cu(II) Binding Increases the Soluble Toxicity of Amyloidogenic Light Chains

TLDR
The data reported here, elucidate the biochemical bases of the Cu2+-induced toxicity and show that copper binding is just one of the several biochemical traits contributing to LC soluble in vivo toxicity.

The Journey of Human Transthyretin: Synthesis, Structure Stability, and Catabolism

TLDR
The aim of the review is to give an overview of the TTR biological life cycle, from its synthesis to its catabolism, and the role of mutations and physiological ligands on the stability of TTR tetramers.

Macromolecular crowding and supersaturation protect hemodialysis patients from the onset of dialysis-related amyloidosis

TLDR
Results indicate that, although the inhibitory effects of sera were deteriorated in long-term dialysis patients, they were ameliorated by maintenance dialysis treatments in the short term, and suggested the importance of monitoring temporary and accumulated risks to prevent the development of amyloidoses in general.

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