Structural properties of apolipoprotein A-I mimetic peptides that promote ABCA1-dependent cholesterol efflux

Abstract Peptides mimicking the major protein of highdensity lipoprotein (HDL), apolipoprotein A-I (apoA-I), are promising therapeutics for cardiovascular diseases. Similar to apoA-I, their atheroprotective property is attributed to their ability to form discoidal HDL-like particles by extracting ce...

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Autores principales:	Rafique M. Islam, Mohsen Pourmousa, Denis Sviridov, Scott M. Gordon, Edward B. Neufeld, Lita A. Freeman, B. Scott Perrin, Richard W. Pastor, Alan T. Remaley
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f6efbe4920c04c43bd95b4e576884d48
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spelling	oai:doaj.org-article:f6efbe4920c04c43bd95b4e576884d482021-12-02T15:08:26ZStructural properties of apolipoprotein A-I mimetic peptides that promote ABCA1-dependent cholesterol efflux10.1038/s41598-018-20965-22045-2322https://doaj.org/article/f6efbe4920c04c43bd95b4e576884d482018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-20965-2https://doaj.org/toc/2045-2322Abstract Peptides mimicking the major protein of highdensity lipoprotein (HDL), apolipoprotein A-I (apoA-I), are promising therapeutics for cardiovascular diseases. Similar to apoA-I, their atheroprotective property is attributed to their ability to form discoidal HDL-like particles by extracting cellular cholesterol and phospholipids from lipid microdomains created by the ABCA1 transporter in a process called cholesterol efflux. The structural features of peptides that enable cholesterol efflux are not well understood. Herein, four synthetic amphipathic peptides denoted ELK, which only contain Glu, Leu, Lys, and sometimes Ala, and which have a wide range of net charges and hydrophobicities, were examined for cholesterol efflux. Experiments show that ELKs with a net neutral charge and a hydrophobic face that subtends an angle of at least 140° are optimal for cholesterol efflux. All-atom molecular dynamics simulations show that peptides that are effective in promoting cholesterol efflux stabilize HDL nanodiscs formed by these peptides by the orderly covering of the hydrophobic acyl chains on the edge of the disc. In contrast to apoA-I, which forms an anti-parallel double belt around the HDL, active peptides assemble in a mostly anti-parallel “picket fence” arrangement. These results shed light on the efflux ability of apoA-I mimetics and inform the future design of such therapeutics.Rafique M. IslamMohsen PourmousaDenis SviridovScott M. GordonEdward B. NeufeldLita A. FreemanB. Scott PerrinRichard W. PastorAlan T. RemaleyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-15 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rafique M. Islam Mohsen Pourmousa Denis Sviridov Scott M. Gordon Edward B. Neufeld Lita A. Freeman B. Scott Perrin Richard W. Pastor Alan T. Remaley Structural properties of apolipoprotein A-I mimetic peptides that promote ABCA1-dependent cholesterol efflux
description	Abstract Peptides mimicking the major protein of highdensity lipoprotein (HDL), apolipoprotein A-I (apoA-I), are promising therapeutics for cardiovascular diseases. Similar to apoA-I, their atheroprotective property is attributed to their ability to form discoidal HDL-like particles by extracting cellular cholesterol and phospholipids from lipid microdomains created by the ABCA1 transporter in a process called cholesterol efflux. The structural features of peptides that enable cholesterol efflux are not well understood. Herein, four synthetic amphipathic peptides denoted ELK, which only contain Glu, Leu, Lys, and sometimes Ala, and which have a wide range of net charges and hydrophobicities, were examined for cholesterol efflux. Experiments show that ELKs with a net neutral charge and a hydrophobic face that subtends an angle of at least 140° are optimal for cholesterol efflux. All-atom molecular dynamics simulations show that peptides that are effective in promoting cholesterol efflux stabilize HDL nanodiscs formed by these peptides by the orderly covering of the hydrophobic acyl chains on the edge of the disc. In contrast to apoA-I, which forms an anti-parallel double belt around the HDL, active peptides assemble in a mostly anti-parallel “picket fence” arrangement. These results shed light on the efflux ability of apoA-I mimetics and inform the future design of such therapeutics.
format	article
author	Rafique M. Islam Mohsen Pourmousa Denis Sviridov Scott M. Gordon Edward B. Neufeld Lita A. Freeman B. Scott Perrin Richard W. Pastor Alan T. Remaley
author_facet	Rafique M. Islam Mohsen Pourmousa Denis Sviridov Scott M. Gordon Edward B. Neufeld Lita A. Freeman B. Scott Perrin Richard W. Pastor Alan T. Remaley
author_sort	Rafique M. Islam
title	Structural properties of apolipoprotein A-I mimetic peptides that promote ABCA1-dependent cholesterol efflux
title_short	Structural properties of apolipoprotein A-I mimetic peptides that promote ABCA1-dependent cholesterol efflux
title_full	Structural properties of apolipoprotein A-I mimetic peptides that promote ABCA1-dependent cholesterol efflux
title_fullStr	Structural properties of apolipoprotein A-I mimetic peptides that promote ABCA1-dependent cholesterol efflux
title_full_unstemmed	Structural properties of apolipoprotein A-I mimetic peptides that promote ABCA1-dependent cholesterol efflux
title_sort	structural properties of apolipoprotein a-i mimetic peptides that promote abca1-dependent cholesterol efflux
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/f6efbe4920c04c43bd95b4e576884d48
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Structural properties of apolipoprotein A-I mimetic peptides that promote ABCA1-dependent cholesterol efflux

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