2jq3

Structure and Dynamics of Human Apolipoprotein C-III

spinqualitylabelsall models 2jq3 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2jq3 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease APOC3_HUMAN Defects in APOC3 are the cause of hyperalphalipoproteinemia type 2 (HALP2) [MIM:614028. HALP2 is a condition characterized by high levels of high density lipoprotein (HDL) and increased HDL cholesterol levels. Function APOC3_HUMAN Inhibits lipoprotein lipase and hepatic lipase and decreases the uptake of lymph chylomicrons by hepatic cells. This suggests that it delays the catabolism of triglyceride-rich particles. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Human apolipoprotein CIII (apoCIII) is a surface component of chylomicrons, very low density lipoproteins, and high density lipoproteins. ApoCIII inhibits lipoprotein lipase as well as binding of lipoproteins to cell surface heparan sulfate proteoglycans and receptors. High levels of apoCIII are often correlated with elevated levels of blood lipids (hypertriglyceridemia). Here, we report the three-dimensional NMR structure and dynamics of human apo-CIII in complex with SDS micelles, mimicking its natural lipid-bound state. Thanks to residual dipolar coupling data, the first detailed view is obtained of the structure and dynamics of an intact apolipoprotein in its lipid-bound state. ApoCIII wraps around the micelle surface as a necklace of six approximately 10-residue amphipathic helices, which are curved and connected via semiflexible hinges. Three positively charged (Lys) residues line the polar faces of helices 1 and 2. Interestingly, their three-dimensional conformation is similar to that of the low density lipoprotein receptor binding motifs of apoE/B and the receptor-associated protein. At the C-terminal side of apoCIII, an array of negatively charged residues lines the polar faces of helices 4 and 5 and the adjacent flexible loop. Sequence comparison shows that this asymmetric charge distribution along the solvent-exposed face of apoCIII as well as other structural features are conserved among mammals. This structure provides a template for exploration of molecular mechanisms by which human apoCIII inhibits lipoprotein lipase and receptor binding. Structure and dynamics of human apolipoprotein CIII.,Gangabadage CS, Zdunek J, Tessari M, Nilsson S, Olivecrona G, Wijmenga SS J Biol Chem. 2008 Jun 20;283(25):17416-27. Epub 2008 Apr 11. PMID:18408013 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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