Role of the C-terminal domain of PCSK9 in degradation of the LDL receptors.

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Role of the C-terminal domain of PCSK9 in degradation of the LDL receptors.
Holla, Oystein L; Cameron, Jamie; Tveten, Kristian; Strøm, Thea Bismo; Berge, Knut Erik; Laerdahl, Jon K; Leren, Trond P
Journal of lipid research 2011, 52 (10):1787-94
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dc.contributor.authorHolla, Oystein Len
dc.contributor.authorCameron, Jamieen
dc.contributor.authorTveten, Kristianen
dc.contributor.authorStrøm, Thea Bismoen
dc.contributor.authorBerge, Knut Eriken
dc.contributor.authorLaerdahl, Jon Ken
dc.contributor.authorLeren, Trond Pen
dc.identifier.citationJournal of lipid research 2011, 52 (10):1787-94en
dc.description.abstractProprotein 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.en
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Endokrinologi: 774en
dc.titleRole of the C-terminal domain of PCSK9 in degradation of the LDL receptors.en
dc.typeJournal articleen
dc.typepeer revieweden
dc.contributor.departmentUnit for Cardiac and Cardiovascular Genetics, Department of Medical Genetics, Centre for Molecular Biology and Neuroscience (CMBN).en
dc.identifier.journalJournal of lipid researchen
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