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Common Fibril Structures Imply Systemically Conserved Protein Misfolding Pathways In Vivo
Author(s) -
Annamalai Karthikeyan,
Liberta Falk,
Vielberg MarieTheres,
Close William,
Lilie Hauke,
Gührs KarlHeinz,
Schierhorn Angelika,
Koehler Rolf,
Schmidt Andreas,
Haupt Christian,
Hegenbart Ute,
Schönland Stefan,
Schmidt Matthias,
Groll Michael,
Fändrich Marcus
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201701761
Subject(s) - fibril , amyloid fibril , amyloidosis , chemistry , protein folding , amyloid (mycology) , biophysics , biochemistry , biology , amyloid β , pathology , medicine , disease , inorganic chemistry
Systemic amyloidosis is caused by the misfolding of a circulating amyloid precursor protein and the deposition of amyloid fibrils in multiple organs. Chemical and biophysical analysis of amyloid fibrils from human AL and murine AA amyloidosis reveal the same fibril morphologies in different tissues or organs of one patient or diseased animal. The observed structural similarities concerned the fibril morphology, the fibril protein primary and secondary structures, the presence of post‐translational modifications and, in case of the AL fibrils, the partially folded characteristics of the polypeptide chain within the fibril. Our data imply for both analyzed forms of amyloidosis that the pathways of protein misfolding are systemically conserved; that is, they follow the same rules irrespective of where inside one body fibrils are formed or accumulated.