title: Apolipoprotein(a) binds to low-density lipoprotein at two distant sites in lipoprotein(a).
abstract: Lipoprotein(a) [Lp(a)] consists of low-density lipoprotein (LDL) and apolipoprotein(a) [apo(a)] linked with a disulfide bond. Scanning force microscopy (SFM) of Lp(a) showed, for the first time, a belt-like structure of apo(a) with both ends attached to a spherical LDL. The two ends of apo(a) were bound to the LDL sphere at two distant sites. Occasionally, the ends were attached to two touching spheres. Under the same imaging conditions, LDL appeared as individual spheres. Electron microscopy (EM) studies of Lp(a) by several groups over the past decade failed to reveal this belt-like structure of apo(a). Images of isolated apo(a) in air or in phosphate buffer showed apo(a) as individual belts, and these belts tended to crowd together. Lp(a) formed leaf-like aggregates; apo(a) aggregates were fishnet-like, whereas LDL aggregates were less characteristic. Quantitative analysis of Lp(a) showed the diameter of the LDL to be 24.8 +/- 8.7 nm (n = 46), which is close to the reported value of 24.2 +/- 4.2 nm found with EM. The length of the belts attached to the spheres was measured to be 173.5 +/- 6.6 nm (n = 15). I also found, by using a functionalized tip, that the interaction force between apo(a) and its ligand, lysine, was related to the ionic strength of the bulk solution. This force can be reduced by the presence of epsilon-aminocaproic acid.
authors.affiliation: Department of Medicine, The University of Chicago, Illinois 60637, USA. shxu@medicine.bsd.uchicago.edu
authors.forename: S
authors.initials: S
authors.lastname: Xu
mesh_terms: D001054:Apolipoproteins A / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D006801:Humans; D008024:Ligands; D017270:Lipoprotein(a) / Q000737:chemistry / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism*; D018625:Microscopy, Atomic Force / Q000379:methods; D012996:Solutions
chemical_list: D001054:Apolipoproteins A; D008024:Ligands; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D012996:Solutions