1by6 | pdb_00001by6
Peptide of human apolipoprotein C-II
Structural highlights
Disease[APOC2_HUMAN] Defects in APOC2 are the cause of hyperlipoproteinemia type 1B (HLPP1B) [MIM:207750]. It is an autosomal recessive trait characterized by hypertriglyceridemia, xanthomas, and increased risk of pancreatitis and early atherosclerosis.[1] Function[APOC2_HUMAN] Component of the very low density lipoprotein (VLDL) fraction in plasma, and is an activator of several triacylglycerol lipases. The association of APOC2 with plasma chylomicrons, VLDL, and HDL is reversible, a function of the secretion and catabolism of triglyceride-rich lipoproteins, and changes rapidly. 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 PubMedWe have studied the three-dimensional structure of a biologically active peptide of apolipoprotein C-II (apoC-II) in the presence of lipid mimetics by CD and NMR spectroscopy. This peptide, corresponding to residues 44-79 of apoC-II, has been shown to reverse the symptoms of genetic apoC-II deficiency in a human subject. A comparison of alpha-proton secondary shifts and CD spectroscopic data indicates that the structure of apoC-II(44-79) is similar in the presence of dodecylphosphocholine and sodium dodecyl sulfate. The three-dimensional structure of apoC-II(44-79) in the presence of sodium dodecyl sulfate, determined by relaxation matrix calculations, contains two amphipathic helical domains formed by residues 50-58 and 67-75, separated by a non-helical linker centered at Tyr63. The C-terminal helix is terminated by a loop formed by residues 76-79. The C-terminal helix is better defined and has a larger hydrophobic face than the N-terminal helix, which leads us to propose that the C-terminal helix together with the non-helical Ile66 constitute the primary lipid binding domain of apoC-II(44-79). Based on our structure we suggest a new mechanism of lipoprotein lipase activation in which both helices of apoC-II(44-79) remain lipid bound, while the seven-residue interhelical linker extends away from the lipid surface in order to project Tyr63 into the apoC-II binding site of lipoprotein lipase. Structure of a biologically active fragment of human serum apolipoprotein C-II in the presence of sodium dodecyl sulfate and dodecylphosphocholine.,Storjohann R, Rozek A, Sparrow JT, Cushley RJ Biochim Biophys Acta. 2000 Jul 19;1486(2-3):253-64. PMID:10903476[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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