These two authors contributed equally.
Special Issue Article
Analysis of the haptoglobin binding region on the apolipoprotein A-I-derived P2a peptide†
Article first published online: 19 FEB 2013
Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.
Journal of Peptide Science
Special Issue: Special issue devoted to contributions presented at the 13th Naples Workshop on Bioactive Peptides, June 7–10, 2012, Naples
Volume 19, Issue 4, pages 220–226, April 2013
How to Cite
Spagnuolo, M. S., Di Stasi, R., De Rosa, L., Maresca, B., Cigliano, L. and D'Andrea, L. D. (2013), Analysis of the haptoglobin binding region on the apolipoprotein A-I-derived P2a peptide. J. Peptide Sci., 19: 220–226. doi: 10.1002/psc.2487
Special issue devoted to contributions presented at the 13th Naples Workshop on Bioactive Peptides, June 7-10, 2012, Naples.
- Issue published online: 24 MAR 2013
- Article first published online: 19 FEB 2013
- Manuscript Accepted: 10 JAN 2013
- Manuscript Revised: 8 JAN 2013
- Manuscript Received: 25 OCT 2012
- helix conformation;
Apolipoprotein A-I (ApoA-I) is the main protein component of the high density lipoproteins and it plays an important role in the reverse cholesterol transport. In particular, it stimulates cholesterol efflux from peripheral cells toward liver and activates the enzyme lecithin-cholesterol acyltransferase (LCAT). Haptoglobin (Hpt), a plasma α2-glycoprotein belonging to the family of acute-phase proteins, binds to ApoA-I inhibiting the stimulation of the enzyme LCAT. Previously, we reported that a synthetic peptide, P2a, binds to and displaces Hpt from ApoA-I restoring the LCAT cholesterol esterification activity in the presence of Hpt. Here, we investigate the molecular determinants underlining the interaction between Hpt and P2a peptide. Analysis of truncated P2a analogs showed that P2a sequence can only be slight reduced in length at the N-terminal to preserve the ability of binding to Hpt. Binding assays showed that charged residues are not involved in Hpt recognition; actually, E146A and D157A substitutions increase the binding affinity to Hpt. Biological characterization of the corresponding P2a peptide analogs, Apo146 and Apo157, showed that the two peptides interfere with Hpt binding to HDL and are more effective than P2a peptide in rescue LCAT activity from Hpt inhibition. This result suggests novel hints to design peptides with anti-atherogenic activity. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.