A. Rozek et al., Conformation of human apolipoprotein C-I in a lipid-mimetic environment determined by CD and NMR spectroscopy, BIOCHEM, 38(44), 1999, pp. 14475-14484
The high-resolution conformation of human apoC-I in complexes with sodium d
odecyl sulfate (SDS) is presented. As estimated from CD data, apoC-I adopts
54% helical secondary structure when bound to SDS, which is similar to the
helical content previously found with phospholipids, The NMR-derived confo
rmation of apoC-I is composed of two amphipathic helices, residues 7-29 and
38-52, separated by a flexible linker. The N-terminal helix contains a mob
ile hinge involving residues 12-15, The hydrophobic side chains cluster on
the nonpolar face of both helices, thus forming two discrete lipid-binding
sites in the N-terminal helix and one in the C-terminal helix. As suggested
by amide proton resonance line widths and deuterium exchange rates, the N-
terminal helix is more flexible and may bind less tightly to the detergent
than the C-terminal helix. The different mobility of both helices appears t
o be related to side-chain composition, rather than length of the amphipath
ic helix, and may play a role in the function of apoC-I as an activator of
lecithin:cholesterol acyltransferase (LCAT), A model is suggested in which
the C-terminal helix serves as a Lipid anchor while the N-terminal helix ma
y hinge off the lipid surface to make specific contacts with LCAT.