title: Relevance of the amino acid conversions L144R (Zaragoza) and L159P (Zavalla) in the apolipoprotein A-I binding site for haptoglobin.
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.
authors.affiliation: Dipartimento delle Scienze Biologiche, Università di Napoli Federico II, I-80134 Napoli, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Cigliano
authors.forename: Luca D
authors.initials: LD
authors.lastname: D'Andrea
authors.forename: Bernardetta
authors.initials: B
authors.lastname: Maresca
authors.forename: Milena
authors.initials: M
authors.lastname: Serino
authors.forename: Alessandro
authors.initials: A
authors.lastname: Carlucci
authors.forename: Alfonso
authors.initials: A
authors.lastname: Salvatore
authors.forename: Maria Stefania
authors.initials: MS
authors.lastname: Spagnuolo
authors.forename: Graziana
authors.initials: G
authors.lastname: Scigliuolo
authors.forename: Carlo
authors.initials: C
authors.lastname: Pedone
authors.forename: Paolo
authors.initials: P
authors.lastname: Abrescia
mesh_terms: D000595:Amino Acid Sequence; D016632:Apolipoprotein A-I / Q000235:genetics* / Q000378:metabolism*; D001665:Binding Sites; D001667:Binding, Competitive; D006242:Haptoglobins / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000037:antagonists & inhibitors; D011485:Protein Binding / Q000187:drug effects
chemical_list: D016632:Apolipoprotein A-I; D006242:Haptoglobins; D008075:Lipoproteins, HDL; D010455:Peptides; D007862:Phosphatidylcholine-Sterol O-Acyltransferase