NMR structure of human apolipoprotein C-II in the presence of sodium dodecyl sulfate.
The structure and protein-detergent interactions of apolipoprotein C-II (apoC-II) in the presence of SDS micelles have been investigated using circular dichroism and heteronuclear NMR techniques applied to (15)N-labeled protein. Micellar SDS, a commonly used mimetic of the lipoprotein surface, inhibits the aggregation of apoC-II and induces a stable structure containing approximately 60% alpha-helix as determined by circular dichroism. NMR reveals the first 12 residues of apoC-II to be structurally heterogeneous and largely disordered, with the rest of the protein forming a predominantly helical structure. Three regions of helical conformation, residues 16-36, 50-56, and 63-77, are well-defined by NMR-derived constraints, with the intervening regions showing more loosely defined helical conformation. The structure of apoC-II is compared to that determined for other apolipoproteins in a similar environment. Our results shed light on the lipid interactions of apoC-II and its mechanism of lipoprotein lipase activation.
MacRaild
C A
CA
Russell Grimwade School of Biochemistry and Molecular Biology, University of Melbourne, Gate 12, Royal Parade, Parkville, Victoria 3052, Australia.
Hatters
D M
DM
Howlett
G J
GJ
Gooley
P R
PR
D000595:Amino Acid Sequence; D053304:Apolipoprotein C-II; D001056:Apolipoproteins C / Q000737:chemistry*; D002352:Carrier Proteins / Q000737:chemistry; D002942:Circular Dichroism; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D006801:Humans; D008823:Micelles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D010446:Peptide Fragments / Q000737:chemistry; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry*
D053304:Apolipoprotein C-II; D001056:Apolipoproteins C; D002352:Carrier Proteins; D008823:Micelles; D010446:Peptide Fragments; D012967:Sodium Dodecyl Sulfate