Three Complement-Type Repeats of the Low-Density Lipoprotein Receptor-Related Protein Define a Common Binding Site for RAP, PAI-1, and Lactoferrin
| Autor: | Brian Vash, Neil Phung, Dianne L. DeCamp, Sima Zein |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Repetitive Sequences
Amino Acid Recombinant Fusion Proteins Allosteric regulation Immunology Binding Competitive Biochemistry Mice Plasminogen Activator Inhibitor 1 Animals Humans LDL-Receptor Related Protein-Associated Protein Receptors Immunologic Scavenger receptor Binding site Cells Cultured Glycoproteins Receptors Lipoprotein Receptors Scavenger Binding Sites biology Lactoferrin Endoplasmic reticulum Membrane Proteins Complement System Proteins Cell Biology Hematology Fibroblasts Scavenger Receptors Class B Peptide Fragments Chaperone (protein) LDL receptor biology.protein Carrier Proteins Low Density Lipoprotein Receptor-Related Protein-1 Protein Binding Protein ligand |
| Zdroj: | Blood. 92:3277-3285 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v92.9.3277.421k50_3277_3285 |
| Popis: | The low-density lipoprotein receptor-related protein (LRP) is a 600-kD scavenger receptor that binds a number of protein ligands with high affinity. Although some ligands do not compete with each other, binding of all is uniformly blocked by the 39-kD receptor-associated protein (RAP). RAP is normally found in the endoplasmic reticulum and seems to function as a chaperone for LRP. To identify the binding sites for RAP, lactoferrin, and plasminogen activator inhibitor-1 (PAI-1), a bacterial expression system has been developed to produce soluble LRP fragments spanning residues 783-1399. These residues overlap most of the CNBr fragment containing the second cluster of complement-type repeats (C). Solid phase binding assays show that 125I-RAP binds to fragments containing three successive complement-type repeats: C5-C7. PAI-1 and lactoferrin bind to the same fragments. A fragment containing C5-C7 also blocks uptake and degradation of 125I-RAP by fibroblasts in a concentration-dependent manner. Binding competition experiments show that RAP, PAI-1, and lactoferrin each inhibit the binding of the others, suggesting that at this site in LRP, RAP acts as a competitive, rather than an allosteric, inhibitor of PAI-1 and lactoferrin binding.© 1998 by The American Society of Hematology. |
| Databáze: | OpenAIRE |
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