Regular Article
The Neuroendocrine Protein 7B2 Acts as a Molecular Chaperone in the in Vitro Folding of Human Insulin-like Growth Factor-I Secreted from Yeast

https://doi.org/10.1006/bbrc.1995.1830Get rights and content

Abstract

The neuroendocrine protein 7B2 prevents premature activation of PC2, an enzyme involved in the processing of prohormones in the secretory pathway. We inquired if this chaperone like function encompasses a broader role for 7B2 in the folding of hormone-like proteins. As a test, the fate of misfolded human insulin like growth factor-1 (IGF1) was assessed, in the presence and absence of 7B2. Most of the recombinant IGF1 molecules, secreted from yeast, are a conglomeration of inactive multimers which are either disulfide-linked or mere physical aggregates. We find that yeast produced 7B2 influences the in vitro conversion of inactive molecules into active monomers. However, the amounts of disulfide-linked dimers remain unaffected during this conversion. Interestingly, both 7B2 and the molecular chaperone DnaK interact with IGF1 in the yeast two hybrid system. Like DnaK, 7B2 also binds the tumor suppressor protein p53. Binding of DnaK to exposed epitopes of aggregated proteins is known to be a prerequisite for deaggregation. It is conceivable that 7B2 participates in an analogous manner in the dissociation of non-covalently linked multimers of IGF1. Our results indicate that 7B2 might find an application in the deaggregation of potentially useful therapeutic proteins.

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