The structure of lipoprotein(a) and ligand-induced conformational changes.
Lipoprotein(a) is composed of low-density lipoprotein linked both covalently and noncovalently to apolipoprotein(a). The structure of lipoprotein(a) and the interactions between low-density lipoprotein and apolipoprotein(a) were investigated by electron microscopy and correlated with analytical ultracentrifugation. Electron microscopy of rotary-shadowed and unidirectionally shadowed lipoprotein(a) prepared without glycerol revealed that it is a nearly spherical particle with no large projections. After extraction of both lipoprotein(a) and low-density lipoprotein with glycerol prior to rotary shadowing, the protein components were observed to consist of a ring of density made up of nodules of different sizes, with apolipoprotein(a) and apolipoprotein B-100 closely associated with each other. However, when lipoprotein(a) was treated with a lysine analogue, 6-aminohexanoic acid, much of the apolipoprotein(a) separated from the apolipoprotein B-100. In 6-aminohexanoic acid-treated preparations without glycerol extraction, lipoprotein(a) particles had an irregular mass of density around the core. In contrast, lipoprotein(a) particles treated with 6-aminohexanoic acid in the presence of glycerol had a long tail, in which individual kringles could be distinguished, extending from the ring of apolipoprotein B-100. The length of the tail was dependent on the particular isoform of apolipoprotein(a). Dissociation of the noncovalent interactions between apolipoprotein(a) and low-density lipoprotein as a result of shear forces or changes in the microenvironment may contribute to selective retention of lipoprotein(a) in the vasculature.
Weisel
J W
JW
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. weisel@mail.cellbio.med.upenn.edu
Nagaswami
C
C
Woodhead
J L
JL
Higazi
A A
AA
Cain
W J
WJ
Marcovina
S M
SM
Koschinsky
M L
ML
Cines
D B
DB
Bdeir
K
K
D008078:Cholesterol, LDL / Q000737:chemistry / Q000648:ultrastructure; D008024:Ligands; D017270:Lipoprotein(a) / Q000737:chemistry* / Q000648:ultrastructure; D008239:Lysine / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry / Q000648:ultrastructure; D014461:Ultracentrifugation
D008078:Cholesterol, LDL; D008024:Ligands; D017270:Lipoprotein(a); D020033:Protein Isoforms; D008239:Lysine