Apoptin induces tumor-specific apoptosis as a globular multimer
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 4531061
Author(s) Leliveld, SR; Zhang, YH; Rohn, JL; Noteborn, MHM; Abrahams, JP
Author(s) at UniBasel Abrahams, Jan Pieter
Year 2003
Title Apoptin induces tumor-specific apoptosis as a globular multimer
Journal JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 278
Number 11
Pages / Article-Number 9042-9051
Mesh terms Science & TechnologyLife Sciences & BiomedicineBiochemistry & Molecular BiologyBiochemistry & Molecular Biology
Abstract

The chicken anemia virus-derived Apoptin protein induces tumor-specific apoptosis. Here, we show that recombinant Apoptin protein spontaneously forms noncovalent globular aggregates comprising 30 to 40 subunits in vitro. This multimerization is robust and virtually irreversible, and the globular aggregates are also stable in cell extracts, suggesting that they remain intact within the cell. Furthermore, studies of Apoptin expressed in living cells confirm that Apoptin indeed exists in large complexes in vivo. We map the structural motifs responsible for multimerization in vitro and aggregation in vivo to the N-terminal half of the protein. Moreover, we show that covalently fixing the Apoptin monomers within the recombinant protein multimer by internal cross-linking does not affect the biological activity of Apoptin, as these fixed aggregates exhibit similar tumor-specific localization and apoptosis-inducing properties as non-cross-linked Apoptin. Taken together, our results imply that recombinant Apoptin protein is a multimer when inducing apoptosis, and we propose that this multimeric state is an essential feature of its ability to do so. Finally, we determine that Apoptin adopts little, if any, regular secondary structure within the aggregates. This surprising result would classify Apoptin as the first protein for which, rather than the formation of a well defined tertiary and quaternary structure, semi-random aggregation is sufficient for activity.

Publisher AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
ISSN/ISBN 0021-9258
Full Text on edoc
Digital Object Identifier DOI 10.1074/jbc.M210803200; 10.1074/jbc.M210803200
ISI-Number WOS:000181524000024
Document type (ISI) Article
   

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