The conformation of a nascent polypeptide inside the ribosome tunnel affects protein targeting and protein folding

Peterson, J.H., Woolhead, C.A. and Bernstein, H.D. (2010) The conformation of a nascent polypeptide inside the ribosome tunnel affects protein targeting and protein folding. Molecular Microbiology, 78(1), pp. 203-217. (doi: 10.1111/j.1365-2958.2010.07325.x) (PMID:20804452) (PMCID:PMC2950912)

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Abstract

In this report, we describe insights into the function of the ribosome tunnel that were obtained through an analysis of an unusual 25 residue N-terminal motif (EspP(1-25)) associated with the signal peptide of the Escherichia coli EspP protein. It was previously shown that EspP(1-25) inhibits signal peptide recognition by the signal recognition particle, and we now show that fusion of EspP(1-25) to a cytoplasmic protein causes it to aggregate. We obtained two lines of evidence that both of these effects are attributable to the conformation of EspP(1-25) inside the ribosome tunnel. First, we found that mutations in EspP(1-25) that abolished its effects on protein targeting and protein folding altered the cross-linking of short nascent chains to ribosomal components. Second, we found that a mutation in L22 that distorts the tunnel mimicked the effects of the EspP(1-25) mutations on protein biogenesis. Our results provide evidence that the conformation of a polypeptide inside the ribosome tunnel can influence protein folding under physiological conditions and suggest that ribosomal mutations might increase the solubility of at least some aggregation-prone proteins produced in E. coli.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Woolhead, Professor Cheryl
Authors: Peterson, J.H., Woolhead, C.A., and Bernstein, H.D.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:Molecular Microbiology
ISSN:0950-382X
ISSN (Online):1365-2958
Published Online:20 August 2010

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
496961Folding and insertion of a bacterial inner membrane proteinCheryl WoolheadBiotechnology and Biological Sciences Research Council (BBSRC)BB/G011281/1Institute of Molecular Cell and Systems Biology