Role of molecular chaperones in inclusion body formation

M. Mar Carrió, Antonio Villaverde

Research output: Contribution to journalArticleResearchpeer-review

75 Citations (Scopus)

Abstract

Protein misfolding and aggregation are linked to several degenerative diseases and are responsible for the formation of bacterial inclusion bodies. Roles of molecular chaperones in promoting protein deposition have been speculated but not proven in vivo. We have investigated the involvement of individual chaperones in inclusion body formation by producing the misfolding-prone but partially soluble VP1LAC protein in chaperone null bacterial strains. Unexpectedly, the absence of a functional GroEL significantly reduced aggregation and favoured the incidence of the soluble protein form, from 4 to 35% of the total VP1LAC protein. On the other hand, no regular inclusion bodies were then formed but more abundant small aggregates up to 0.05 μm3. Contrarily, in a DnaK- background, the amount of inclusion body protein was 2.5-fold higher than in the wild-type strain and the average volume of the inclusion bodies increased from 0.25 to 0.38 μm3. Also in the absence of DnaK, the minor fraction of soluble protein appears as highly proteolytically stable, suggesting an inverse connection between proteolysis and aggregation managed by this chaperone. In summary, GroEL and DnaK appear as major antagonist controllers of inclusion body formation by promoting and preventing, respectively, the aggregation of misfolded polypeptides. GroEL might have, in addition, a key role in driving the protein transit from the soluble to the insoluble cell fraction and also in the opposite direction. Although chaperones ClpB, ClpA, IbpA and IbpB also participate in these processes, the impact of the respective null mutations on bacterial inclusion body formation is much more moderate. © 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.
Original languageEnglish
Pages (from-to)215-221
JournalFEBS Letters
Volume537
DOIs
Publication statusPublished - 27 Feb 2003

Keywords

  • Chaperone
  • DnaK
  • Escherichia coli
  • GroEL
  • Inclusion body
  • Protein aggregation

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