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Abstract

The amyloidoses are a group of protein misfolding diseases in which the precursor protein undergoes a conformational change that triggers the formation of amyloid fibrils in different tissues and organs, causing cell death and organ failure. Amyloidoses can be either localized or systemic. In localized amyloidosis, amyloid deposits form at the site of precursor protein synthesis, whereas in systemic amyloidosis, amyloid deposition occurs distant from the site of precursor protein secretion. We review the type of proteins and cells involved and what is known about the complex pathophysiology of these diseases. We focus on light chain amyloidosis to illustrate how biochemical and biophysical studies have led to a deeper understanding of the pathogenesis of this devastating disease. We also review current cellular, tissue, and animal models and discuss the challenges and opportunities for future studies of the systemic amyloidoses.

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Systemic Amyloidoses: Video 1
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/content/journals/10.1146/annurev-biochem-072611-130030
2013-06-02
2024-04-13
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Supplemental Material

    This morph animation shows the transition among three unique dimer orientations present in the crystal structures of κI O18/O8 and AL-09, as well as the nuclear magnetic resonance structure of κI Y87H, to demonstrate the structural differences between them. This animation does not represent genuine conformational changes. The residues in monomer A involved in the κI dimer interface are in magenta, whereas residues outside the dimer interface are in cyan. Monomer B (ribbons) of AL-09 (, PDB code: 2Q1E), κI O18/O8 (, PDB code: 2Q20), and κI Y87H (, PDB code: 2KQM) shows a ∼90° and ∼180° rotation with respect to the monomer A from the canonical dimer interface. In yellow ribbon are shown the differences in dimer structures, like the hands on a clock moving in intervals of 90°. Interface residues Q3, Y36, F98, and Q100 () show the biggest conformational differences between dimer interfaces.

  • Article Type: Review Article
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