2QTW

The Crystal Structure of PCSK9 at 1.9 Angstroms Resolution Reveals structural homology to Resistin within the C-terminal domain

2QTW の概要

• エントリーDOI: 10.2210/pdb2qtw/pdb
• 分子名称: Proprotein convertase subtilisin/kexin type 9 Propeptide, Proprotein convertase subtilisin/kexin type 9, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: pro-protein convertase, coronary heart disease, hypercholesterolemia, low density lipoprotein receptor, autocatalytic cleavage, cholesterol metabolism, disease mutation, glycoprotein, hydrolase, lipid metabolism, phosphorylation, protease, secreted, serine protease, steroid metabolism, zymogen
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 72553.64

構造登録者

Hampton, E.N.,Knuth, M.W.,Li, J.,Harris, J.L.,Lesley, S.A.,Spraggon, G. (登録日: 2007-08-02, 公開日: 2007-09-18, 最終更新日: 2024-10-16)

主引用文献

Hampton, E.N.,Knuth, M.W.,Li, J.,Harris, J.L.,Lesley, S.A.,Spraggon, G.
The self-inhibited structure of full-length PCSK9 at 1.9 A reveals structural homology with resistin within the C-terminal domain.
Proc.Natl.Acad.Sci.Usa, 104:14604-14609, 2007

PubMed 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.

PubMed: 17804797
DOI: 10.1073/pnas.0703402104

実験手法

X-RAY DIFFRACTION (1.9 Å)