Apoptin induces tumor-specific apoptosis as a globular multimer

Leliveld, Sirik R. and Zhang, Ying-Hui and Rohn, Jennifer L. and Noteborn, Mathieu H. M. and Abrahams, Jan Pieter. (2003) Apoptin induces tumor-specific apoptosis as a globular multimer. Journal of Biological Chemistry, 278 (11). pp. 9042-9051.

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Official URL: https://edoc.unibas.ch/75977/

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Nano-diffraction of Biological Specimen (Abrahams)
UniBasel Contributors:Abrahams, Jan Pieter
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Society for Biochemistry and Molecular Biology
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:05 Nov 2020 15:19
Deposited On:05 Nov 2020 15:19

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