Bajari, Tarek M. and Lindstedt, Ken A. and Riepl, Michael and Mirsky, Vladimir M. and Nimpf, Johannes and Wolfbeis, Otto S. and Dresel, Hans A. and Bautz, Ekkehard K. F. and Schneider, Wolfgang Johann (1998) A minimal binding domain of the low density lipoprotein receptor family. BIOLOGICAL CHEMISTRY, 379 (8-9). pp. 1053-1062. ISSN 1431-6730, 1437-4315
Full text not available from this repository.Abstract
As more relatives of the low density lipoprotein receptor (LDLR) are discovered, defining their minimal binding domain(s) becomes a challenge. Here we have chosen the multifunctional chicken oocyte receptor for yolk deposition (termed LR8), and the pan-receptor ligand, receptor associated protein (RAP), as model systems to characterize a minireceptor using the phage display approach. Displayed fragments derived from the entire 819 residue LR8 molecule, followed by selection via panning on RAP, led to the definition of an 80 residue stretch LR8 minireceptor. It contains 12 cysteines, and represents parts of the second, the entire third, and parts of the fourth, of the eight clustered 'ligand binding repeats' in LR8; only two of the eight stretches of negatively charged residues of LR8, i.e., EDGSDE and DSGEDEE, are present. The latter sequence is reminiscent of that in the fifth repeat of the human LDLR, thought to be most critical for interaction with positive charge clusters in ligands. Baculovirus-mediated expression of the soluble minireceptor in insect cells showed it to fold as a monomer, and sulfhydryl-reduction-sensitive interaction with RAP was demonstrated for immobilized as well as soluble minireceptor. Furthermore, the LR8-derived minireceptor provided a RAP-responsive surface when covalently coupled to the surface of a gold electrode. In addition to its use in defining minimal binding domains, the phage display approach provides powerful tools for dissection, and consequently, manipulation, of the function of receptors so as to direct their binding activity toward ligands of diagnostic and/or therapeutic interest.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHICKEN OOCYTE RECEPTOR; PROTEIN ALPHA-2-MACROGLOBULIN RECEPTOR; LDL-RECEPTOR; LIGAND-BINDING; APOLIPOPROTEIN-E; MULTIFUNCTIONAL RECEPTOR; MONOCLONAL-ANTIBODIES; PLASMINOGEN-ACTIVATOR; FILAMENTOUS PHAGE; 39-KDA PROTEIN; ligand binding; low density lipoprotein; phage display; receptor; oocyte |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Analytische Chemie, Chemo- und Biosensorik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Feb 2023 09:21 |
| Last Modified: | 23 Feb 2023 09:21 |
| URI: | https://pred.uni-regensburg.de/id/eprint/49617 |
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