Specificity Determinants in the Interaction of Apolipoprotein(a) Kringles with Tetranectin and LDL
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N. R. Caterer
Abstract
Lipoprotein(a) is composed of low density lipoprotein and apolipoprotein(a). Apolipoprotein(a) has evolved from plasminogen and contains 10 different plasminogen kringle 4 homologous domains [KIV(1 110)]. Previous studies indicated that lipoprotein(a) noncovalently binds the Nterminal region of lipoprotein B100 and the plasminogen kringle 4 binding plasma protein tetranectin. In this study recombinant KIV(2), KIV(7) and KIV(10) derived from apolipoprotein(a) were produced in E. coli and the binding to tetranectin and low density lipoprotein was examined. Only KIV(10) bound to tetranectin and binding was similar to that of plasminogen kringle 4 to tetranectin. Only KIV(7) bound to LDL. In order to identify the residues responsible for the difference in specificity between KIV(7) and KIV(10), a number of surfaceexposed residues located around the lysine binding clefts were exchanged. Ligand binding analysis of these derivatives showed that Y62, and to a minor extent W32 and E56, of KIV(7) are important for LDL binding to KIV(7), whereas R32 and D56 of KIV(10) are required for tetranectin binding of KIV(10).
Copyright © 2002 by Walter de Gruyter GmbH & Co. KG
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Articles in the same Issue
- Pigment Epithelium-Derived Factor (PEDF), a Serpin with Potent Anti-Angiogenic and Neurite Outgrowth-promoting Properties
- Mechanism of Inhibition of RNA Polymerase I Transcription by DNA-dependent Protein Kinase
- Evidence for Haploinsufficiency of the Human HNF1α Gene Revealed by Functional Characterization of MODY3-Associated Mutations
- In vitro and in vivo Stability of the 2ζ2 Protein Complex of the Broad Host-Range Streptococcus pyogenes pSM19035 Addiction System
- Effects of Antineoplastic Agents on Cytoplasmic and Membrane-Bound Heat Shock Protein 70 (Hsp70) Levels
- Characterization of the VPS10 Domain of SorLA/LR11 as Binding Site for the Neuropeptide HA
- Substrate Specificity and Inhibitor Studies of a Membrane-Bound Ganglioside Sialidase Isolated from Human Brain Tissue
- Specificity Determinants in the Interaction of Apolipoprotein(a) Kringles with Tetranectin and LDL
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- Application of Peptides Containing the Cleavage Sequence of Pro-TNFα in Assessing TACE Activity of Whole Cells
