The structure and interactions of human apolipoprotein C-II in dodecyl phosphocholine.
The structure of human apolipoprotein C-II (apoC-II) in the presence of dodecyl phosphocholine (DPC) micelles has been investigated by NMR spectroscopy. The resulting structural information is compared to that available for apoC-II in the presence of sodium dodecyl sulfate, revealing a high level of overall similarity but several significant differences. These findings further our understandings of the structural basis for apoC-II function. The interactions of the protein with the detergent micelle are probed using intermolecular nuclear Overhauser effects (NOEs) and paramagnetic agents. These interactions are seen across almost the full length of apoC-II and show the periodicity expected for an amphipathic helix interacting with the amphipathic surface of the DPC micelle. Furthermore, we observe specific contacts between lysine residues of apoC-II and protons near the phosphate group of DPC, consistent with the predictions of the so-called "snorkel hypothesis" of the structural basis for the apolipoprotein/lipid interaction (Segrest, J. P., Jackson, R. L., Morrisett, J. D., and Gotto, A. M., Jr. (1974) A molecular theory of lipid-protein interactions in the plasma lipoproteins, FEBS Lett 38, 247-258.). These findings offer the most detailed structural information available for the interaction between an apolipoprotein and the phospholipids of the lipoprotein surface and provide the first direct structural support for the snorkel hypothesis.
MacRaild
Christopher A
CA
Russell Grimwade School of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
Howlett
Geoffrey J
GJ
Gooley
Paul R
PR
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D053304:Apolipoprotein C-II; D001056:Apolipoproteins C / Q000737:chemistry* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000737:chemistry; D006801:Humans; D008345:Manganese / Q000737:chemistry; D008823:Micelles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism*; D017433:Protein Structure, Secondary; D013113:Spin Labels
D000596:Amino Acids; D053304:Apolipoprotein C-II; D001056:Apolipoproteins C; D001426:Bacterial Proteins; D003497:Cyclic N-Oxides; D008823:Micelles; D013113:Spin Labels; D010767:Phosphorylcholine; C037404:12-doxylstearic acid; C005072:5-doxylstearic acid; D008345:Manganese; C028810:dodecylphosphocholine