Functional characterization of T7 and T8 of human apolipoprotein (a).
Lipoprotein (a) [Lp(a)], a risk factor for coronary artery disease, is a LDL-like particle with apolipoprotein (a) [apo(a)] covalently linked to apolipoprotein B (apoB). Apo(a) has many repeats of kringle 4-like domain, classified as type 1 through type 10 (T1-T10). Deletion analysis was performed to define the functional modules of human apo(a). We found that T7 has an affinity for cell surfaces and is required for Lp(a) formation. Cell surface binding was inhibited by L-proline, KI = 4.7 +/- 3.6 mM (n=3). We also found that T8 has an affinity for subendothelial extracellular matrix (ECM). ECM binding was inhibited modestly by L-proline (KI = 6.1 +/- 1.9 mM, n=3), and more effectively by L-lysine (KI = 2.7 +/- 1.0 mM, n=3) and its analogue, 6-aminohexanoic acid (KI = 0.35 +/- 0.13 mM, n=3). These data point to T7 and T8 as important functional modules of apo(a).
Trieu
V N
VN
Department of Medicine and Department of Biochemistry, University of North Texas Health Science Center-Fort Worth, Fort Worth, Texas, 76107, USA. vtrieu@hi.org
McConathy
W J
WJ
D000818:Animals; D001054:Apolipoproteins A / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D016466:CHO Cells; D006224:Cricetinae; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D018082:Kringles / Q000502:physiology; D017270:Lipoprotein(a) / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D014407:Tumor Cells, Cultured
D001054:Apolipoproteins A; D016326:Extracellular Matrix Proteins; D017270:Lipoprotein(a); D008565:Membrane Proteins; D020033:Protein Isoforms