Effects of Protein Corona on IAPP Amyloid Aggregation, Fibril Remodelling, and Cytotoxicity

Abstract Aggregation of islet amyloid polypeptide (IAPP), a peptide hormone co-synthesized and co-stored with insulin in pancreatic cells and also co-secreted to the circulation, is associated with beta-cell death in type-2 diabetes (T2D). In T2D patients IAPP is found aggregating in the extracellul...

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Autores principales:	Emily H. Pilkington, Yanting Xing, Bo Wang, Aleksandr Kakinen, Miaoyi Wang, Thomas P. Davis, Feng Ding, Pu Chun Ke
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/eaaee3cf9e0345d29278a7ad9b05f984
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spelling	oai:doaj.org-article:eaaee3cf9e0345d29278a7ad9b05f9842021-12-02T15:05:19ZEffects of Protein Corona on IAPP Amyloid Aggregation, Fibril Remodelling, and Cytotoxicity10.1038/s41598-017-02597-02045-2322https://doaj.org/article/eaaee3cf9e0345d29278a7ad9b05f9842017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02597-0https://doaj.org/toc/2045-2322Abstract Aggregation of islet amyloid polypeptide (IAPP), a peptide hormone co-synthesized and co-stored with insulin in pancreatic cells and also co-secreted to the circulation, is associated with beta-cell death in type-2 diabetes (T2D). In T2D patients IAPP is found aggregating in the extracellular space of the islets of Langerhans. Although the physiological environments of these intra- and extra-cellular compartments and vascular systems significantly differ, the presence of proteins is ubiquitous but the effects of protein binding on IAPP aggregation are largely unknown. Here we examined the binding of freshly-dissolved IAPP as well as pre-formed fibrils with two homologous proteins, namely cationic lysozyme (Lys) and anionic alpha-lactalbumin (aLac), both of which can be found in the circulation. Biophysical characterizations and a cell viability assay revealed distinct effects of Lys and aLac on IAPP amyloid aggregation, fibril remodelling and cytotoxicity, pointing to the role of protein “corona” in conferring the biological impact of amyloidogenic peptides. Systematic molecular dynamics simulations further provided molecular and structural details for the observed differential effects of proteins on IAPP amyloidosis. This study facilitates our understanding of the fate and transformation of IAPP in vivo, which are expected to have consequential bearings on IAPP glycemic control and T2D pathology.Emily H. PilkingtonYanting XingBo WangAleksandr KakinenMiaoyi WangThomas P. DavisFeng DingPu Chun KeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Emily H. Pilkington Yanting Xing Bo Wang Aleksandr Kakinen Miaoyi Wang Thomas P. Davis Feng Ding Pu Chun Ke Effects of Protein Corona on IAPP Amyloid Aggregation, Fibril Remodelling, and Cytotoxicity
description	Abstract Aggregation of islet amyloid polypeptide (IAPP), a peptide hormone co-synthesized and co-stored with insulin in pancreatic cells and also co-secreted to the circulation, is associated with beta-cell death in type-2 diabetes (T2D). In T2D patients IAPP is found aggregating in the extracellular space of the islets of Langerhans. Although the physiological environments of these intra- and extra-cellular compartments and vascular systems significantly differ, the presence of proteins is ubiquitous but the effects of protein binding on IAPP aggregation are largely unknown. Here we examined the binding of freshly-dissolved IAPP as well as pre-formed fibrils with two homologous proteins, namely cationic lysozyme (Lys) and anionic alpha-lactalbumin (aLac), both of which can be found in the circulation. Biophysical characterizations and a cell viability assay revealed distinct effects of Lys and aLac on IAPP amyloid aggregation, fibril remodelling and cytotoxicity, pointing to the role of protein “corona” in conferring the biological impact of amyloidogenic peptides. Systematic molecular dynamics simulations further provided molecular and structural details for the observed differential effects of proteins on IAPP amyloidosis. This study facilitates our understanding of the fate and transformation of IAPP in vivo, which are expected to have consequential bearings on IAPP glycemic control and T2D pathology.
format	article
author	Emily H. Pilkington Yanting Xing Bo Wang Aleksandr Kakinen Miaoyi Wang Thomas P. Davis Feng Ding Pu Chun Ke
author_facet	Emily H. Pilkington Yanting Xing Bo Wang Aleksandr Kakinen Miaoyi Wang Thomas P. Davis Feng Ding Pu Chun Ke
author_sort	Emily H. Pilkington
title	Effects of Protein Corona on IAPP Amyloid Aggregation, Fibril Remodelling, and Cytotoxicity
title_short	Effects of Protein Corona on IAPP Amyloid Aggregation, Fibril Remodelling, and Cytotoxicity
title_full	Effects of Protein Corona on IAPP Amyloid Aggregation, Fibril Remodelling, and Cytotoxicity
title_fullStr	Effects of Protein Corona on IAPP Amyloid Aggregation, Fibril Remodelling, and Cytotoxicity
title_full_unstemmed	Effects of Protein Corona on IAPP Amyloid Aggregation, Fibril Remodelling, and Cytotoxicity
title_sort	effects of protein corona on iapp amyloid aggregation, fibril remodelling, and cytotoxicity
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/eaaee3cf9e0345d29278a7ad9b05f984
work_keys_str_mv	AT emilyhpilkington effectsofproteincoronaoniappamyloidaggregationfibrilremodellingandcytotoxicity AT yantingxing effectsofproteincoronaoniappamyloidaggregationfibrilremodellingandcytotoxicity AT bowang effectsofproteincoronaoniappamyloidaggregationfibrilremodellingandcytotoxicity AT aleksandrkakinen effectsofproteincoronaoniappamyloidaggregationfibrilremodellingandcytotoxicity AT miaoyiwang effectsofproteincoronaoniappamyloidaggregationfibrilremodellingandcytotoxicity AT thomaspdavis effectsofproteincoronaoniappamyloidaggregationfibrilremodellingandcytotoxicity AT fengding effectsofproteincoronaoniappamyloidaggregationfibrilremodellingandcytotoxicity AT puchunke effectsofproteincoronaoniappamyloidaggregationfibrilremodellingandcytotoxicity
_version_	1718388928924352512

Effects of Protein Corona on IAPP Amyloid Aggregation, Fibril Remodelling, and Cytotoxicity

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