The solution structure of an apoA-I deletion mutant, apoA-I(1-186) was dete
rmined by the chemical shift index (CSI) method and the torsion angle likel
ihood obtained from shift and sequence similarity (TALOS) method, using het
eronuclear multidimensional NMR spectra of [u-C-13, u-N-15, u-50% H-2]apoA-
I(1-186) in the presence of sodium dodecyl sulfate (SDS), The backbone reso
nances mere assigned from a combination of triple-resonance data (HNCO, HNC
A, HN(CO)CA, HN(CA)CO and HN(COCA)HA), and intraresidue and sequential NOEs
(three-dimensional (3D) and four-dimensional (4D) C-13- and N-15-edited NO
ESY). Analysis of the NOEs, H-alpha, C-alpha and C' chemical shifts shows t
hat apoA-I(1-186) in lipid-mimetic solution is composed of ol-helices (whic
h include the residues 8-32, 45-64, 67-77, 83-87, 90-97, 100-140, 146- 162,
and 166-181), interrupted by short irregular segments. There is one relati
vely long, irregular and mostly flexible region (residues 33-44), that sepa
rates the N-terminal domain (residues 1-32) from the main body of protein.
In addition, we report, for the first time, the structure of the N-terminal
domain of apoA-I in a lipid-mimetic environment. Its structure (alpha -hel
ix 8-32 and flexible linker 33-44) mould suggest that this domain is struct
urally, and possibly functionally, separated from the other part of the mol
ecule. (C) 2001 Federation of European Biochemical Societies. Published by
Elsevier Science B.V. All rights reserved.