Protein Engineering vol. 9 no. 3 pp. 307-313, 1996
© 1996 Oxford University Press
RESEARCH-ARTICLE |
Synthethic collagen-like domain derived from the macrophage scavenger receptor binds acetylated low-density lipoprotein in vitro
1Protein Engineering Research Institute 6–2–3, Furuedai, Suita, Osaka 565 4Third Department of Internal Medicine, University of Tokyo Tokyo 113 5Faculty of Pharmaceutical Sciences, Osaka University 1–6 Yamada-oka, Suita, Osaka 565 Japan
3To whom correspondence should be addressed
The bovine macrophage scavenger receptor is a 70 kDa membrane protein that is trimerized on the macrophage cell surface. The receptor binds modified low-density lipoproteins (LDL). The core binding site is located within 22 residues at the C-terminus of the collagen-like domain of the receptor. The Lys residue at position 337 plays an important role in ligand binding. Here, the collagen-like domain was constructed using a peptide architecture technique, in which three collagenous peptide chains were crosslinked at their N-termini. The crosslinked peptide showed a collagen-like structure by circular dichroism and existed mainly in a monomeric triple helical form as shown by gel exclusion chromatography. The triple-stranded peptide was demonstrated to bind acetylated LDL (Ac-LDL) using regions derived from Gly323 to Lys340 of the natural bovine scavenger receptor. However, a single-stranded peptide with the same amino acid sequence did not bind Ac-LDL. Furthermore, a triple-stranded mutated peptide in which Lys corresponding to Lys337 in the mother protein was substituted with Ala showed no binding activity to Ac-LDL. These results, taken together, indicate that the synthetic collagen-tike peptide has a similar structure to the binding site in the scavenger receptor, and support the view that the collagen-tike domain of the natural scavenger receptor recognizes Ac-LDL.
Keywords: acetylated-LDL binding/chemical ligation/circular dichroism spectra/collagen structure/gel filtration
Received October 19, 1995; revised December 4, 1995; accepted December 18, 1995.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. L. Lauer-Fields, K. A. Tuzinski, K.-i. Shimokawa, H. Nagase, and G. B. Fields Hydrolysis of Triple-helical Collagen Peptide Models by Matrix Metalloproteinases J. Biol. Chem., April 28, 2000; 275(18): 13282 - 13290. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. J. de Winther, K. W. van Dijk, L. M. Havekes, and M. H. Hofker Macrophage Scavenger Receptor Class A : A Multifunctional Receptor in Atherosclerosis Arterioscler Thromb Vasc Biol, February 1, 2000; 20(2): 290 - 297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Deprez and N. C. Inestrosa Molecular modeling of the collagen-like tail of asymmetric acetylcholinesterase Protein Eng. Des. Sel., January 1, 2000; 13(1): 27 - 34. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. G. Lysko, J. Weinstock, C. L. Webb, M. E. Brawner, and N. A. Elshourbagy Identification of a Small-Molecule, Nonpeptide Macrophage Scavenger Receptor Antagonist J. Pharmacol. Exp. Ther., June 1, 1999; 289(3): 1277 - 1285. [Abstract] [Full Text]
|
|
|
|
|
|
L. Andersson and M. W. Freeman Functional Changes in Scavenger Receptor Binding Conformation Are Induced by Charge Mutants Spanning the Entire Collagen Domain J. Biol. Chem., July 31, 1998; 273(31): 19592 - 19601. [Abstract] [Full Text] [PDF]
|
|