Structure of a biologically active fragment of human serum apolipoprotein C-II in the presence of sodium dodecyl sulfate and dodecylphosphocholine.
We 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.
Storjohann
R
R
Institute of Molecular Biology and Biochemistry and Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
Rozek
A
A
Sparrow
J T
JT
Cushley
R J
RJ
D000595:Amino Acid Sequence; D053304:Apolipoprotein C-II; D001056:Apolipoproteins C / Q000097:blood / Q000737:chemistry*; D002942:Circular Dichroism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry*; D010767:Phosphorylcholine / Q000031:analogs & derivatives; D011487:Protein Conformation; D012967:Sodium Dodecyl Sulfate
D053304:Apolipoprotein C-II; D001056:Apolipoproteins C; D010446:Peptide Fragments; C412003:apolipoprotein C-II (44-79); D010767:Phosphorylcholine; D012967:Sodium Dodecyl Sulfate; C028810:dodecylphosphocholine