Relevance of the amino acid conversions L144R (Zaragoza) and L159P (Zavalla) in the apolipoprotein A-I binding site for haptoglobin

Luisa Cigliano, Luca D. D'Andrea, Bernardetta Maresca, Milena Serino, Alessandro Carlucci, Alfonso Salvatore, Maria Stefania Spagnuolo, Graziana Scigliuolo, Carlo Pedone, Paolo Abrescia

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The high-density lipoprotein apolipoprotein A-I (ApoA-I) stimulates the enzyme lecithin-cholesterol acyltransferase (LCAT) in the reverse cholesterol transport pathway. Two ApoA-I variants, Zaragoza (L144R) and Zavalla (L159P), are associated with low levels of HDL-cholesterol but normal LCAT activity. Haptoglobin interacts with ApoA-I, impairing LCAT stimulation. Synthetic peptides matching the haptoglobin-binding site of native or variant ApoA-I (native, P2a; variants, Zav-pep and Zar-pep) bound haptoglobin with different activity: Zar-pep>P2a>Zav-pep. They also differently rescued LCAT in vitro activity in the presence of haptoglobin (P2a=Zar-pep>Zav-pep). Therefore, both amino acid conversions affect haptoglobin binding and LCAT regulation. We highlight the role of haptoglobin in LCAT regulation in subjects with ApoA-I variants.

Original languageEnglish
Pages (from-to)1421-1426
Number of pages6
JournalBiological Chemistry
Volume389
Issue number11
DOIs
Publication statusPublished - Nov 1 2008

Fingerprint

Phosphatidylcholine-Sterol O-Acyltransferase
Haptoglobins
Apolipoprotein A-I
Binding Sites
Amino Acids
HDL Lipoproteins
HDL Cholesterol
apolipoprotein A-I Zavalla
Cholesterol
Peptides
Enzymes

Keywords

  • ApoA-I Zaragoza
  • ApoA-I Zavalla
  • High-density lipoprotein
  • Lecithin-cholesterol acyltransferase
  • Peptides
  • Reverse cholesterol transport

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology

Cite this

Cigliano, L., D'Andrea, L. D., Maresca, B., Serino, M., Carlucci, A., Salvatore, A., ... Abrescia, P. (2008). Relevance of the amino acid conversions L144R (Zaragoza) and L159P (Zavalla) in the apolipoprotein A-I binding site for haptoglobin. Biological Chemistry, 389(11), 1421-1426. https://doi.org/10.1515/BC.2008.156

Relevance of the amino acid conversions L144R (Zaragoza) and L159P (Zavalla) in the apolipoprotein A-I binding site for haptoglobin. / Cigliano, Luisa; D'Andrea, Luca D.; Maresca, Bernardetta; Serino, Milena; Carlucci, Alessandro; Salvatore, Alfonso; Spagnuolo, Maria Stefania; Scigliuolo, Graziana; Pedone, Carlo; Abrescia, Paolo.

In: Biological Chemistry, Vol. 389, No. 11, 01.11.2008, p. 1421-1426.

Research output: Contribution to journalArticle

Cigliano, L, D'Andrea, LD, Maresca, B, Serino, M, Carlucci, A, Salvatore, A, Spagnuolo, MS, Scigliuolo, G, Pedone, C & Abrescia, P 2008, 'Relevance of the amino acid conversions L144R (Zaragoza) and L159P (Zavalla) in the apolipoprotein A-I binding site for haptoglobin', Biological Chemistry, vol. 389, no. 11, pp. 1421-1426. https://doi.org/10.1515/BC.2008.156
Cigliano, Luisa ; D'Andrea, Luca D. ; Maresca, Bernardetta ; Serino, Milena ; Carlucci, Alessandro ; Salvatore, Alfonso ; Spagnuolo, Maria Stefania ; Scigliuolo, Graziana ; Pedone, Carlo ; Abrescia, Paolo. / Relevance of the amino acid conversions L144R (Zaragoza) and L159P (Zavalla) in the apolipoprotein A-I binding site for haptoglobin. In: Biological Chemistry. 2008 ; Vol. 389, No. 11. pp. 1421-1426.
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