| abstract |
The present invention relates to the construction and use of small multimerization devices, preferably of human origin, which self-assemble fused functional domains to multimeric and multifunctional complexes. Multimerization devices of this invention do not significantly interfere with secretion, expression yields and the independent folding of functional domains, which are attached via flexible but protease-resistant linkers. Modular gene cassettes encoding functional domains, linkers and multimerization domain can easily be combined to a cistron encoding the multimeric protein. Translation in a suitable host results in self-assembly to multimers larger than dimers. In cases, in which one or both functional domains are not expressible in sufficient yields or native fold in the same expression host, multimeric proteins can be produced, in which one or both functional domains or the multimerization device are produced separately by, e.g., in vitro translation, peptide synthesis and/or refolding and subsequently, e.g., chemically coupled to the remaining part of the multimeric protein. |