Browse views: by Year, by Function, by GLF, by Subfunction, by Conference, by Journal

The self-inhibited structure of full-length PCSK9 at 1.9 A reveals structural homology with resistin within the C-terminal domain.

Hampton, Eric and Knuth, Mark and Li, Jun and Harris, Jennifer and Lesley, Scott and Spraggon, Glen (2007) The self-inhibited structure of full-length PCSK9 at 1.9 A reveals structural homology with resistin within the C-terminal domain. Proceedings of the National Academy of Sciences of the United States of America, 104 (37). pp. 14604-14609. ISSN 0027-8424

Abstract

Mutations in proprotein convertase subtilisin/kexin type 9 (PCSK9) are strongly associated with levels of low-density lipoprotein cholesterol in the blood plasma and, thereby, occurrence or resistance to atherosclerosis and coronary heart disease. Despite this importance, relatively little is known about the biology of PCSK9. Here, the crystal structure of a full-length construct of PCSK9 solved to 1.9-A resolution is presented. The structure contains a fully folded C-terminal cysteine-rich domain (CRD), showing a distinct structural similarity to the resistin homotrimer, a small cytokine associated with obesity and diabetes. This structural relationship between the CRD of PCSK9 and the resistin family is not observed in primary sequence comparisons and strongly suggests a distant evolutionary link between the two molecules. This three-dimensional homology provides insight into the function of PCSK9 at the molecular level and will help to dissect the link between PCSK9 and CHD.

Item Type: Article
Related URLs:
Additional Information: free final full text version available at publisher's official URL and at PubMedCentral; author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords: hypercholesterolemia, low-density lipoprotein receptor, proprotein convertase, x-ray crystallography, adipocytokine
Related URLs:
Date Deposited: 14 Dec 2009 14:05
Last Modified: 31 Jan 2013 01:27
URI: https://oak.novartis.com/id/eprint/109

Search

Email Alerts

Register with OAK to receive email alerts for saved searches.