2p4e
From Proteopedia
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Crystal Structure of PCSK9
Overview
Proprotein convertase subtilisin kexin type 9 (PCSK9) lowers the abundance, of surface low-density lipoprotein (LDL) receptor through an undefined, mechanism. The structure of human PCSK9 shows the subtilisin-like, catalytic site blocked by the prodomain in a noncovalent complex and, inaccessible to exogenous ligands, and that the C-terminal domain has a, novel fold. Biosensor studies show that PCSK9 binds the extracellular, domain of LDL receptor with K(d) = 170 nM at the neutral pH of plasma, but, with a K(d) as low as 1 nM at the acidic pH of endosomes. The D374Y, gain-of-function mutant, associated with hypercholesterolemia and, early-onset cardiovascular disease, binds the receptor 25 times more, tightly than wild-type PCSK9 at neutral pH and remains exclusively in a, high-affinity complex at the acidic pH. PCSK9 may diminish LDL receptors, by a mechanism that requires direct binding but not necessarily receptor, proteolysis.
About this Structure
2P4E is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia., Cunningham D, Danley DE, Geoghegan KF, Griffor MC, Hawkins JL, Subashi TA, Varghese AH, Ammirati MJ, Culp JS, Hoth LR, Mansour MN, McGrath KM, Seddon AP, Shenolikar S, Stutzman-Engwall KJ, Warren LC, Xia D, Qiu X, Nat Struct Mol Biol. 2007 May;14(5):413-9. Epub 2007 Apr 15. PMID:17435765
Page seeded by OCA on Wed Jan 23 13:57:12 2008
Categories: Homo sapiens | Single protein | Cunningham, D. | Danley, D.E. | Geoghegan, F.K. | Griffor, M.C. | Hawkins, J.L. | Qiu, X. | HG | Endocytosis | Ldl | Ldl receptor | Protease | Subtilisin
