Immunoelectron microscopy of low density lipoproteins yields a ribbon and bow model for the conformation of apolipoprotein B on the lipoprotein surface.
In the present study, the relative positions of 11 anti-apolipoprotein B monoclonal antibodies have been mapped onto the surface of human low density lipoproteins by electron microscopy. As the epitopes recognized by these antibodies have been previously located on the primary sequence of apoB, these data provide a map of the configuration of the protein on the surface of the LDL. The first 89% of apoB-100 may be modeled as a thick ribbon that wraps once around the LDL, completing the encirclement by about amino acid residue 4050. The thickness of the ribbon is sufficient to penetrate the monolayer, so that it makes contact with the core. There is a kink in the ribbon beginning almost halfway along its length at approximately apoB-48. The C-terminal 11% of apoB constitutes the "bow," an elongated structure of about 480 residues, beginning at 4050 and stretching back into one hemisphere and then crossing the ribbon into the other hemisphere between residues 3000 to 3500, thus bringing sequences in the C-terminal portion of apoB-100 near to the suggested binding site for the LDL receptor. The C-terminal sequences may act as a negative regulator of LDL receptor binding, in agreement with Parhofer et al, 1992. J. Clin. Invest. 89: 1931-1937, who reported the enhanced clearance from plasma of apoB-89-containing lipoproteins. It is proposed that in VLDL the bow could function to inhibit binding to the receptor; during lipolysis to form LDL, it is suggested that these C-terminal inhibitory sequences forming the bow would move sufficiently to allow interaction with the LDL-receptor.
Chatterton
J E
JE
Department of Chemistry and Biochemistry, University of California, Los Angeles 90095, USA.
Phillips
M L
ML
Curtiss
L K
LK
Milne
R
R
Fruchart
J C
JC
Schumaker
V N
VN
D000911:Antibodies, Monoclonal; D001055:Apolipoproteins B / Q000737:chemistry* / Q000276:immunology; D001666:Binding Sites, Antibody; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D018604:Epitope Mapping; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000276:immunology; D016253:Microscopy, Immunoelectron; D011487:Protein Conformation; D012984:Software
D000911:Antibodies, Monoclonal; D001055:Apolipoproteins B; D008077:Lipoproteins, LDL