The proteosomal degradation of fusion proteins cannot be predicted from the proteosome susceptibility of their individual components

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Title The proteosomal degradation of fusion proteins cannot be predicted from the proteosome susceptibility of their individual components
Author Ilyinskii, Petr O.; Meriin, Anatoli B.; Gabai, Vladimir L.; Usachev, Evgeny; Prilipov, Alexei G.; Thoidis, Galini; Schnieder, Alexander M.
Journal Name Protein Science
Year Published 2008
Place of publication USA
Publisher Wiley-Blackwell Publishing, Inc.
Abstract It is assumed that the proteosome-processing characteristics of fusion constructs can be predicted from the sum of the proteosome sensitivity of their components. In the present study, we observed that a fusion construct consisting of proteosome-degradable proteins does not necessarily result in a proteosomedegradable chimera. Conversely, fusion of proteosome-resistant proteins may result in a proteosomedegradable composite. We previously demonstrated that conserved influenza proteins can be unified into a single fusion antigen that is protective, and that vaccination with combinations of proteosome-resistant and proteosome-degradable antigens resulted in an augmented T-cell response. In the present study we constructed proteosome-degradable mutants of conserved influenza proteins NP, M1, NS1, and M2. These were then fused into multipartite proteins in different positions. The stability and degradation profiles of these fusion constructs were demonstrated to depend on the relative position of the individual proteins within the chimeric molecule. Combining unstable sequences of either NP and M1 or NS1 and M2 resulted in either rapidly proteosome degraded or proteosome-resistant bipartite fusion mutants. However, further unification of the proteosome-degradable forms into a single four-partite fusion molecule resulted in relatively stable chimeric proteins. Conversely, the addition of proteosome-resistant wild-type M2 to proteosomeresistant NP–M1–NS1 fusion protein lead to the decreased stability of the resulting four-partite multigene products, which in one case was clearly proteosome dependent. Additionally, a highly destabilized form of M1 failed to destabilize the wild-type NP. Collectively, we did not observe any additive effect leading to proteosomal degradation/nondegradation of a multigene construct.
Peer Reviewed Yes
Published Yes
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Copyright Statement Self-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the author[s] for more information.
Volume 17
Issue Number 6
Page from 1077
Page to 1085
ISSN 0961-8368
Date Accessioned 2010-03-24
Language en_AU
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Biochemistry and Cell Biology
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1x

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