NDLI: Cys4057 of apolipoprotein(a) is essential for lipoprotein(a) assembly.

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Cys4057 of apolipoprotein(a) is essential for lipoprotein(a) assembly.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kraft, H. G. Müller, H. J. Brunner, C. Utermann, G.
Description	Author Affiliation: Brunner C ( Department of Molecular Pharmacology, Boehringer Mannheim GmbH, Mannheim, Germany.);
Abstract	Lipoprotein(a) contains one copy each of apolipoprotein B-100 and apolipoprotein(a). It has been hypothesized that a disulfide bond might exist between Cys4057 of apolipoprotein(a) and Cys3734 in apolipoprotein B-100. To investigate the role of Cys4057 for lipoprotein(a) assembly, wild-type and in vitro mutagenized apolipoprotein(a) cDNA plasmids were expressed in the human hepatocarcinoma line HepG2. The mutant plasmids encoded apolipoprotein(a) species with Cys4057 exchanged to either serine or glycine. Untransfected HepG2 cells, although able to secrete apolipoprotein B-100-containing lipoproteins, do not synthesize detectable amounts of apolipoprotein(a). After transfection of wild-type plasmid, almost all apolipoprotein(a) in the culture supernatant was present in lipoprotein(a)-like particles as demonstrated by immunoblotting, density-gradient centrifugation, and ELISA. The same analysis performed with supernatants of cells transfected with plasmids mutated in codon 4057 revealed free apolipoprotein(a) glycoprotein without detectable amounts of lipoprotein-associated apolipoprotein(a). Our results strongly suggest the existence of a disulfide bridge between Cys4057 of apolipoprotein(a) and apolipoprotein B-100 within recombinant lipoprotein(a) particles. Furthermore, they indicate that disulfide bridge formation is essential for assembly of the lipoprotein(a)-like complex produced by HepG2 cells and suggest a similar role of Cys4057 during lipoprotein(a) assembly in vivo.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	24
Volume Number	90
Language	English
Publisher	National Academy of Sciences
Publisher Date	1993-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Apolipoproteins Metabolism Cysteine Lipoprotein(a) Biosynthesis Amino Acid Sequence Isolation & Purification Apoprotein(a) Carcinoma, Hepatocellular Cell Line DNA Primers Enzyme-Linked Immunosorbent Assay Immunoblotting Liver Neoplasms Molecular Sequence Data Mutagenesis, Site-Directed Poly A Polymerase Chain Reaction Protein Conformation RNA RNA, Messenger Recombinant Proteins Restriction Mapping Tumor Cells, Cultured Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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