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Intracellular processing of pre-a-inhibitor
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
1999 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Pre-α-inhibitor (PαI) is a plasma protein consisting of a 25 and a 75 kDa polypeptide: bikunin and heavy chain 3 (H3), respectively. Both these polypeptides are made by hepatocytes and while passing through the Golgi complex, bikunin, which carries a chondroitin sulfate chain, becomes covalently linked to the C-terminal amino acid residue of H3 via its polysaccharide. Both bikunin and H3 are made as precursors which are proteolytically cleaved during their intracellular transport. In this thesis, the intracellular processing of these precursors, as well as their assembly to PαI were studied in more detail.

When H3 and bikunin were co-expressed in COS-1 cells, the two polypeptide became coupled. Furthermore, another chondroitin sulfate bearing protein, decorin, was found to form a linkage when co-expressed with H3. These results show that cells other than hepatocytes are capable of forming the protein-glycosaminoglycan link and that the bikunin polypeptide is not required for this coupling to occur. Thus it is possible that non-hepatic cells may produce proteins with similar structures.

Heavy chain 3 is synthesized with a 30 kDa C-terminal extension which is released in the Golgi complex; the cleavage of this propeptide occurs between an Asp and a Pro residue. Transfected COS-1 cells were found to secrete partially cleaved H3. Incubation of this recombinant protein at pH 6.0 or below, led to further cleavage. The reaction seemed to be intramolecular since dilution or immobilization of the protein did not affect the cleavage rate. Mutation or deletionsof the C-terminal extension abolished cleavage suggesting that it is mediated by this part of the polypeptide.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 1999. , 45 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 892
Keyword [en]
Biochemistry, pre-alpha-inhibitor, heavy chain 3, bikunin, intracellular processing
Keyword [sv]
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Medical Biochemistry
URN: urn:nbn:se:uu:diva-407ISBN: 91-554-4610-8OAI: oai:DiVA.org:uu-407DiVA: diva2:164216
Public defence
1999-12-15, Föreläsningssal C103:05, Biomedicinskt Centrum (BMC), Uppsala, Uppsala, 13:15
Available from: 1999-11-24 Created: 1999-11-24Bibliographically approved

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