NMR structure of human apolipoprotein C-II in the presence of sodium dodecyl sulfate

The structure and protein-detergent interactions of apolipoprotein C-II (ap oC-II) in the presence of SDS micelles have been investigated using circula r dichroism and heteronuclear NMR techniques applied to N-15-labeled protei n. Micellar SDS, a commonly used mimetic of the lipoprotein surface, inhibi ts the aggregation of apoC-II and induces a stable structure containing app roximately 60% alpha -helix as determined by circular dichroism. NMR reveal s the first 12 residues of apoC-II to be structurally heterogeneous and lar gely disordered, with the rest of the protein forming a predominantly helic al structure, Three regions of helical conformation, residues 16-36, 50-56, and 63-77, are well-defined by NMR-derived constraints, with the interveni ng regions showing more loosely defined helical conformation. The structure of apoC-II is compared to that determined for other apolipoproteins in a s imilar environment. Our results shed light on the lipid interactions of apo C-II and its mechanism of lipoprotein lipase activation.