Analysis of the haptoglobin binding region on the apolipoprotein A-I-derived P2a peptide(467 views) Spagnuolo MS, Di Stasi R, De Rosa L, Maresca B, Cigliano L, D'Andrea LD
Keywords: Apoa-I, Haptoglobin, Helix Conformation, Lcat, Apolipoprotein 141 161, Apolipoprotein 144 164, Apolipoprotein 146 164, Cardiovascular Agent, High Density Lipoprotein, Phosphatidylcholine Sterol Acyltransferase, Protein P 2a, Synthetic Peptide, Unclassified Drug, Amino Acid Sequence, Amino Terminal Sequence, Article, Binding Affinity, Controlled Study, Drug Binding Site, Drug Design, Drug Protein Binding, Drug Structure, Enzyme Activity, Priority Journal, Protein Analysis, Protein Protein Interaction, Protein Structure, Amino Acid Substitution, Anti-Bacterial Agents, Apolipoprotein A-I, Cholesterol, Female, Humans, Phosphatidylcholine-Sterol O-Acyltransferase,
Affiliations: *** IBB - CNR ***
Istituto per il Sistema Produzione Animale in Ambiente Mediterraneo, CNR, via Argine 1085, Napoli, Italy
Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 16, Napoli, Italy
Dipartimento delle Scienze Biologiche, Università di Napoli 'Federico II', Via Mezzocannone 8, Napoli, Italy
References: Not available.
Analysis of the haptoglobin binding region on the apolipoprotein A-I-derived P2a peptide
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 2-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 (c) 2013 European Peptide Society and John Wiley & Sons, Ltd.
Analysis of the haptoglobin binding region on the apolipoprotein A-I-derived P2a peptide
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Analysis of the haptoglobin binding region on the apolipoprotein A-I-derived P2a peptide