University of Oulu

Biterova, E., Esmaeeli, M., Alanen, H., Saaranen, M., Ruddock, L. (2018) Structures of Angptl3 and Angptl4, modulators of triglyceride levels and coronary artery disease. Scientific Reports, 8 (1), . doi:10.1038/s41598-018-25237-7

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

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Author: Biterova, Ekaterina1; Esmaeeli, Mariam1,2; Alanen, Heli I.1;
Organizations: 11Faculty of Biochemistry and Molecular Biology and Biocenter Oulu, University of Oulu, Oulu, 90220, Finland
2Present address: Department of Molecular Enzymology, University of Potsdam, 14476, Potsdam, Germany
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 4.2 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2018060625413
Language: English
Published: Springer Nature, 2018
Publish Date: 2018-06-06
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 diseas

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Series: Scientific reports
ISSN: 2045-2322
ISSN-E: 2045-2322
ISSN-L: 2045-2322
Volume: 8
Article number: 6752
DOI: 10.1038/s41598-018-25237-7
OADOI: https://oadoi.org/10.1038/s41598-018-25237-7
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Subjects:
Funding: This work was supported by the Academy of Finland (grant numbers 266457 and 272573), Sigrid Juselius Foundation and Biocenter Oulu.
Academy of Finland Grant Number: 272573
Detailed Information: 272573 (Academy of Finland Funding decision)
Dataset Reference: Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-018-25237-7.
  http://dx.doi.org/10.1038/s41598-018-25237-7
Copyright information: © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
  https://creativecommons.org/licenses/by/4.0/