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Aggregation, Protein

  1. Jeannine M. Yon

Published Online: 15 SEP 2006

DOI: 10.1002/3527600906.mcb.200300085

Encyclopedia of Molecular Cell Biology and Molecular Medicine

Encyclopedia of Molecular Cell Biology and Molecular Medicine

How to Cite

Yon, J. M. 2006. Aggregation, Protein. Encyclopedia of Molecular Cell Biology and Molecular Medicine. .

Author Information

  1. Université de Paris-sud, Orsay, France

Publication History

  1. Published Online: 15 SEP 2006

Abstract

Protein misfolding and aggregation are frequent phenomena that occur under different conditions in vivo as well as in vitro. Aggregation is a serious problem affecting both the production of proteins in the biotechnology and pharmaceutical industries and human health. The aggregates are formed from nonnative proteins through intermolecular interactions that compete with intramolecular interactions. There is thus a kinetic competition between proper folding and misfolding, which can generate aggregates.

Recent evidence for transient association of intermediates during in vitro refolding has been obtained for several monomeric proteins. Irreversible and insoluble aggregates are formed in an off-pathway folding process; their formation is concentration dependent and could be prevented by using very small protein concentrations. These aggregates can dissociate and dissolve only in the presence of high concentrations of denaturant. The mechanisms involved in these aggregation processes will be discussed in light of the so-called new view of protein folding.

The environmental conditions within cells are markedly different from those used in in vitro refolding studies. In the production of recombinant proteins in foreign hosts, the formation of disordered aggregates, that is, inclusion bodies, is often observed. However, aggregation can also result in the formation of amyloid fibrils, which are ordered aggregates. These amyloid formations are at the origin of serious diseases.

Keywords:

  • Aggregates;
  • Amyloid Fibrils;
  • Inclusion Bodies;
  • Molecular Chaperones;
  • Protein Folding;
  • Three dimensional–Domain Swapping