Proteolytic processing of human preproapolipoprotein A-I. A proposed defect in the conversion of pro A-I to A-I in Tangier's disease

Jeffrey I Gordon; Harold F Sims; Steven R Lentz; Celina Edelstein; Angelo M Scanu; Arnold W Strauss

doi:10.1016/S0021-9258(18)32773-X

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Proteolytic processing of human preproapolipoprotein A-I. A proposed defect in the conversion of pro A-I to A-I in Tangier's disease

Journal article

Open access

Peer reviewed

Proteolytic processing of human preproapolipoprotein A-I. A proposed defect in the conversion of pro A-I to A-I in Tangier's disease

Jeffrey I Gordon, Harold F Sims, Steven R Lentz, Celina Edelstein, Angelo M Scanu and Arnold W Strauss

The Journal of biological chemistry, Vol.258(6), pp.4037-4044

03/25/1983

DOI: 10.1016/S0021-9258(18)32773-X

PMID: 6300070

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Abstract

The primary translation product of human intestinal apolipoprotein A-I mRNA was isolated from wheat germ and ascites cell-free translation systems. Comparison of its NH2-terminal sequence with that of plasma high density lipoprotein-associated A-I showed that it is initially synthesized as a preproprotein. Like rat preproapolipoprotein A-I, it contains an 18-amino acid prepeptide and a 6-amino acid propeptide. The highly unusual COOH-terminal Gln-Gln dipeptide present in the rat pro-segment is also represented at the same position in the human sequence. The functional division of the 24-amino acid NH2-terminal extention into pro- and presegments was verified by finding that the stable intracellular form of A-I in a human hepatoma cell line was the proprotein. Edman degradation of radiolabeled intracellular and extracellular A-I indicated that this apolipoprotein was secreted without proteolytic cleavage of its hexapeptide prosegment. Therefore, it appears that apolipoprotein A-I undergoes an additional proteolytic processing step before it is fully integrated into plasma high density lipoprotein. Two-dimensional gel electrophoresis of purified proapolipoprotein A-I isolated from the hepatocyte cell culture media indicated that it corresponds to isoforms 2 and 3, the basic A-I isoproteins which are the precursors of plasma A-I and the predominant plasma A-I isoforms found in patients with Tangier's disease (Zannis, V. I., Lees, A. M., Lees, R. S., and Breslow, J. L. (1982) J. Biol. Chem., 257, 4978-4986). Therefore this pathologic state probably arises from a defect in the conversion of proapolipoprotein A-I to apolipoprotein A-I.

Amino Acid Sequence

Cell Line

Protein Biosynthesis

Lipoproteins, HDL - genetics

Protein Precursors - genetics

Tangier Disease - genetics

Species Specificity

Apolipoproteins A

Humans

Liver - metabolism

RNA, Messenger - genetics

Rats

Hypolipoproteinemias - genetics

Jejunum - metabolism

Triticum - metabolism

Plants - metabolism

Animals

Apolipoproteins - genetics

Apolipoprotein A-I

Liver Neoplasms - metabolism

Carcinoma, Hepatocellular - metabolism

Details

Title: Subtitle: Proteolytic processing of human preproapolipoprotein A-I. A proposed defect in the conversion of pro A-I to A-I in Tangier's disease
Creators: Jeffrey I Gordon
Harold F Sims
Steven R Lentz
Celina Edelstein
Angelo M Scanu
Arnold W Strauss
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.258(6), pp.4037-4044
DOI: 10.1016/S0021-9258(18)32773-X
PMID: 6300070
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Grant note: AM 20407 / NIADDK NIH HHS HL 18577 / NHLBI NIH HHS AM 30292 / NIADDK NIH HHS
Language: English
Date published: 03/25/1983
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984094580802771

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