Research Article | Published:

Specific aggregation of partially folded polypeptide chains: The molecular basis of inclusion body composition

Nature Biotechnologyvolume 14pages12831287 (1996) | Download Citation

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Abstract

During expression of many recombinant proteins, off-pathway association of partially folded intermediates into inclusion bodies competes with productive folding. A common assumption is that such aggregation reactions are nonspecific processes. The multimeric intermediates along the aggregation pathway have been identified for both the P22 tailspike and P22 coat protein. We show that for a mixture of proteins refolding in vitro, folding intermediates do not coaggregate with each other but only with themselves. This indicates that aggregation occurs by specific interaction of certain conformations of folding intermediates rather than by nonspecific coaggregation, providing a rationale for recovering relatively pure protein from the inclusion body state.

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Author notes

    • Margaret A. Speed

    Present address: Amgen, Inc., 1840 DeHavilland Dr., Thousand Oaks, CA, 91320

  1. Jonathan King: e-mail: jaking@mit.edu

Affiliations

  1. Biotechnology Process Engineering Center, Massachusetts Institute of Technology, Cambridge, MA, 02139

    • Daniel I. C. Wang
    •  & Jonathan King

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https://doi.org/10.1038/nbt1096-1283

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