The two main competing models for the structure of discoidal lipoprotein A-
I complexes both presume that the protein component is helical and situated
around the perimeter of a lipid bilayer disc. However, the more popular "p
icket fence" model orients the protein helices perpendicular to the surface
of the lipid bilayer, while the alternative "belt" model orients them para
llel to the bilayer surface. To distinguish between these models, we have i
nvestigated the structure of human lipoprotein A-I using a novel form of po
larized internal reflection infrared spectroscopy that can characterize the
relative orientation of protein and lipid components in the lipoprotein co
mplexes under native conditions. Our results verify lipid bilayer structure
in the complexes and point unambiguously to the belt model.