Journal article
Chameleon 'aggregation-prone' segments of apoA-I: A model of amyloid fibrils formed in apoA-I amyloidosis
NN Louros, PL Tsiolaki, MDW Griffin, GJ Howlett, SJ Hamodrakas, VA Iconomidou
International Journal of Biological Macromolecules | ELSEVIER | Published : 2015
Abstract
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-hel..
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Funding Acknowledgements
We should like to thank Dr. Evangelia Chrysina for help with the X-ray experiments and the Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation for allowing us to use the X-ray protein crystallography facility. The help of Dr. George Baltatzis and Prof. Efstratios Patsouris and the use of the Morgagni Microscope at the 1st Department of Pathology, Medical School, University of Athens are also gratefully acknowledged. The authors sincerely thank the Editor in Chief and the Managing Editor for properly handling this manuscript and the anonymous reviewers for their very useful and constructive criticism, which helped us to improve the manuscript. We also thank the University of Athens for support.