文章基本信息

标题：Role of the C-terminal domain of PCSK9 in degradation of the LDL receptors
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作者：Øystein L. Holla ; Jamie Cameron ; Kristian Tveten 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2011
卷号：52
期号：10
页码：1787-1794
DOI：10.1194/jlr.M018093
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low density lipoprotein receptor (LDLR) at the cell surface and disrupts the normal recycling of the LDLR. In this study, we investigated the role of the C-terminal domain for the activity of PCSK9. Experiments in which conserved residues and histidines on the surface of the C-terminal domain were mutated indicated that no specific residues of the C-terminal domain, apart from those responsible for maintaining the overall structure, are required for the activity of PCSK9. Rather, the net charge of the C-terminal domain is important. The more positively charged the C-terminal domain, the higher the activity toward the LDLR. Moreover, replacement of the C-terminal domain with an unrelated protein of comparable size led to significant activity of the chimeric protein.We conclude that the role of the evolutionary, poorly conserved C-terminal domain for the activity of PCSK9 reflects its overall positive charge and size and not the presence of specific residues involved in protein-protein interactions.
关键词：proprotein convertase subtilisin/kexin type 9 ; endosomes ; recycling ; sorting ; low density lipoprotein