title: Electron-microscopic and hydrodynamic characterization of recombinant apolipoprotein (a) and its association with LDL.
abstract: A recombinant apo(a) containing 17 kringle 4 domains as well as the kringle 5 and protease domains of apo(a) was characterized by hydrodynamic studies and electron microscopy. Recombinant apo(a) is a monomer in solution with a molecular weight of 325,000 by sedimentation equilibrium and 320,000 by sedimentation and diffusion, and it is a highly asymmetric molecule with a frictional ratio of 2.2. In the electron microscope recombinant apo(a) is visualized as a flexible chain of domains approximately 800 A long. Sedimentation velocity studies also demonstrate that when it is mixed with LDL, recombinant apo(a) reversibly forms an Lp(a)-like complex with a 1:1 stoichiometry; moreover, complex formation is inhibited by 6-amino hexanoic acid. Hydrodynamic modeling and electron microscopy suggest that only a small portion of the r-apo(a) molecule interacts with the LDL and the rest of the chain extends into solution. Preliminary studies indicate that recombinant apo(a) also binds mouse LDL.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles 90024.
authors.forename: M L
authors.initials: ML
authors.lastname: Phillips
authors.forename: A V
authors.initials: AV
authors.lastname: Lembertas
authors.forename: V N
authors.initials: VN
authors.lastname: Schumaker
authors.forename: R M
authors.initials: RM
authors.lastname: Lawn
authors.forename: S J
authors.initials: SJ
authors.lastname: Shire
authors.forename: T F
authors.initials: TF
authors.lastname: Zioncheck
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure*; D053241:Apoprotein(a); D006801:Humans; D066298:In Vitro Techniques; D018082:Kringles; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL / Q000378:metabolism*; D051379:Mice; D008854:Microscopy, Electron; D008970:Molecular Weight; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D012996:Solutions; D014461:Ultracentrifugation
chemical_list: D001053:Apolipoproteins; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D011994:Recombinant Proteins; D012996:Solutions; D053241:Apoprotein(a)