TY - JOUR
T1 - Chameleon 'aggregation-prone' segments of apoA-I
T2 - A model of amyloid fibrils formed in apoA-I amyloidosis
AU - Louros, Nikolaos N.
AU - Tsiolaki, Paraskevi L.
AU - Griffin, Michael D.W.
AU - Howlett, Geoffrey J.
AU - Hamodrakas, Stavros J.
AU - Iconomidou, Vassiliki A.
N1 - Publisher Copyright:
© 2015 Elsevier B.V.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - Apolipoprotein A-I (apoA-I) is the major component of high density lipoproteins and plays a vital role in reverse cholesterol transport. Lipid-free apoA-I is the main constituent of amyloid deposits found in atherosclerotic plaques, an acquired type of amyloidosis, whereas its N-terminal fragments have been associated with a hereditary form, known as familial apoA-I amyloidosis. Here, we identified and verified four "aggregation-prone" segments of apoA-I with amyloidogenic properties, utilizing electron microscopy, X-ray fiber diffraction, ATR FT-IR spectroscopy and polarized light microscopy. These segments may act as conformational switches, possibly controlling the transition of the α-helical apoA-I content into the "cross-β" architecture of amyloid fibrils. A structural model illuminating the structure of amyloid fibrils formed by the N-terminal fragments of apoA-I is proposed, indicating that two of the identified chameleon segments may play a vital part in the formation of amyloid fibrils in familial apoA-I amyloidosis.
AB - Apolipoprotein A-I (apoA-I) is the major component of high density lipoproteins and plays a vital role in reverse cholesterol transport. Lipid-free apoA-I is the main constituent of amyloid deposits found in atherosclerotic plaques, an acquired type of amyloidosis, whereas its N-terminal fragments have been associated with a hereditary form, known as familial apoA-I amyloidosis. Here, we identified and verified four "aggregation-prone" segments of apoA-I with amyloidogenic properties, utilizing electron microscopy, X-ray fiber diffraction, ATR FT-IR spectroscopy and polarized light microscopy. These segments may act as conformational switches, possibly controlling the transition of the α-helical apoA-I content into the "cross-β" architecture of amyloid fibrils. A structural model illuminating the structure of amyloid fibrils formed by the N-terminal fragments of apoA-I is proposed, indicating that two of the identified chameleon segments may play a vital part in the formation of amyloid fibrils in familial apoA-I amyloidosis.
KW - "Aggregation-prone" peptide-analogues
KW - Amyloid fibrils
KW - Familial apolipoprotein A-I amyloidosis
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U2 - 10.1016/j.ijbiomac.2015.05.032
DO - 10.1016/j.ijbiomac.2015.05.032
M3 - Article
C2 - 26049118
AN - SCOPUS:84930940771
SN - 0141-8130
VL - 79
SP - 711
EP - 718
JO - International Journal of Biological Macromolecules
JF - International Journal of Biological Macromolecules
ER -