Specific aggregation of partially folded polypeptide chains: the molecular basis of inclusion body composition.
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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Biotechnology Process Engineering Center, Massachusetts Institute of Technology, Cambridge 02139, USA.
Wang
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King
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D017100:Bacteriophage P22 / Q000737:chemistry; D001709:Biotechnology; D002213:Capsid / Q000737:chemistry; D006026:Glycoside Hydrolases / Q000737:chemistry; D002479:Inclusion Bodies / Q000737:chemistry*; D046911:Macromolecular Substances; D008956:Models, Chemical; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D017376:Viral Tail Proteins / Q000737:chemistry
D046911:Macromolecular Substances; D010455:Peptides; D017376:Viral Tail Proteins; D006026:Glycoside Hydrolases; C083268:tailspike protein, bacteriophage