Polymerization mechanism of polypeptide chain aggregation.
The misfolding of polypeptide chains and aggregation into the insoluble inclusion body state is a serious problem for biotechnology and biomedical research. Developing a rational strategy to control aggregation requires understanding the mechanism of polymerization. We investigated the in vitro aggregation of P22 tailspike polypeptide chains by classical light scattering, nondenaturing gel electrophoresis, two-dimensional polyacrylamide gel electrophoresis (PAGE), and computer simulations. The aggregation of polypeptide chains during refolding occurred by multimeric polymerization, in which two multimers of any size could associate to form a larger aggregate and did not require a sequential addition of monomeric subunits. The cluster-cluster polymerization mechanism of aggregation is an important determinant in the kinetic competition between productive folding and inclusion body formation. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 54: 333-343, 1997.
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Biotechnology Process Engineering Center, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
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Wang
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