Structures of Angptl3 and Angptl4, modulators of triglyceride levels and coronary artery disease

Abstract Coronary artery disease is the most common cause of death globally and is linked to a number of risk factors including serum low density lipoprotein, high density lipoprotein, triglycerides and lipoprotein(a). Recently two proteins, angiopoietin-like protein 3 and 4, have emerged from genet...

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Autores principales:	Ekaterina Biterova, Mariam Esmaeeli, Heli I. Alanen, Mirva Saaranen, Lloyd W. Ruddock
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4b52b49cf90646698db345f847aeac53
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spelling	oai:doaj.org-article:4b52b49cf90646698db345f847aeac532021-12-02T12:32:10ZStructures of Angptl3 and Angptl4, modulators of triglyceride levels and coronary artery disease10.1038/s41598-018-25237-72045-2322https://doaj.org/article/4b52b49cf90646698db345f847aeac532018-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25237-7https://doaj.org/toc/2045-2322Abstract Coronary artery disease is the most common cause of death globally and is linked to a number of risk factors including serum low density lipoprotein, high density lipoprotein, triglycerides and lipoprotein(a). Recently two proteins, angiopoietin-like protein 3 and 4, have emerged from genetic studies as being factors that significantly modulate plasma triglyceride levels and coronary artery disease. The exact function and mechanism of action of both proteins remains to be elucidated, however, mutations in these proteins results in up to 34% reduction in coronary artery disease and inhibition of function results in reduced plasma triglyceride levels. Here we report the crystal structures of the fibrinogen-like domains of both proteins. These structures offer new insights into the reported loss of function mutations, the mechanisms of action of the proteins and open up the possibility for the rational design of low molecular weight inhibitors for intervention in coronary artery disease.Ekaterina BiterovaMariam EsmaeeliHeli I. AlanenMirva SaaranenLloyd W. RuddockNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ekaterina Biterova Mariam Esmaeeli Heli I. Alanen Mirva Saaranen Lloyd W. Ruddock Structures of Angptl3 and Angptl4, modulators of triglyceride levels and coronary artery disease
description	Abstract Coronary artery disease is the most common cause of death globally and is linked to a number of risk factors including serum low density lipoprotein, high density lipoprotein, triglycerides and lipoprotein(a). Recently two proteins, angiopoietin-like protein 3 and 4, have emerged from genetic studies as being factors that significantly modulate plasma triglyceride levels and coronary artery disease. The exact function and mechanism of action of both proteins remains to be elucidated, however, mutations in these proteins results in up to 34% reduction in coronary artery disease and inhibition of function results in reduced plasma triglyceride levels. Here we report the crystal structures of the fibrinogen-like domains of both proteins. These structures offer new insights into the reported loss of function mutations, the mechanisms of action of the proteins and open up the possibility for the rational design of low molecular weight inhibitors for intervention in coronary artery disease.
format	article
author	Ekaterina Biterova Mariam Esmaeeli Heli I. Alanen Mirva Saaranen Lloyd W. Ruddock
author_facet	Ekaterina Biterova Mariam Esmaeeli Heli I. Alanen Mirva Saaranen Lloyd W. Ruddock
author_sort	Ekaterina Biterova
title	Structures of Angptl3 and Angptl4, modulators of triglyceride levels and coronary artery disease
title_short	Structures of Angptl3 and Angptl4, modulators of triglyceride levels and coronary artery disease
title_full	Structures of Angptl3 and Angptl4, modulators of triglyceride levels and coronary artery disease
title_fullStr	Structures of Angptl3 and Angptl4, modulators of triglyceride levels and coronary artery disease
title_full_unstemmed	Structures of Angptl3 and Angptl4, modulators of triglyceride levels and coronary artery disease
title_sort	structures of angptl3 and angptl4, modulators of triglyceride levels and coronary artery disease
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/4b52b49cf90646698db345f847aeac53
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Structures of Angptl3 and Angptl4, modulators of triglyceride levels and coronary artery disease

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