Trigger factor in complex with the ribosome forms a molecular cradle for nascent proteins

Nature. 2004 Sep 30;431(7008):590-6. doi: 10.1038/nature02899. Epub 2004 Aug 29.

Abstract

During protein biosynthesis, nascent polypeptide chains that emerge from the ribosomal exit tunnel encounter ribosome-associated chaperones, which assist their folding to the native state. Here we present a 2.7 A crystal structure of Escherichia coli trigger factor, the best-characterized chaperone of this type, together with the structure of its ribosome-binding domain in complex with the Haloarcula marismortui large ribosomal subunit. Trigger factor adopts a unique conformation resembling a crouching dragon with separated domains forming the amino-terminal ribosome-binding 'tail', the peptidyl-prolyl isomerase 'head', the carboxy-terminal 'arms' and connecting regions building up the 'back'. From its attachment point on the ribosome, trigger factor projects the extended domains over the exit of the ribosomal tunnel, creating a protected folding space where nascent polypeptides may be shielded from proteases and aggregation. This study sheds new light on our understanding of co-translational protein folding, and suggests an unexpected mechanism of action for ribosome-associated chaperones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallization
  • Crystallography, X-Ray
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / metabolism*
  • Haloarcula marismortui
  • Hydrophobic and Hydrophilic Interactions
  • Models, Genetic
  • Models, Molecular
  • Molecular Chaperones / chemistry
  • Molecular Chaperones / metabolism
  • Peptidylprolyl Isomerase / chemistry*
  • Peptidylprolyl Isomerase / metabolism*
  • Protein Binding
  • Protein Biosynthesis*
  • Protein Conformation
  • Protein Folding*
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Proteins / chemistry
  • Proteins / metabolism*
  • Ribosomes / chemistry
  • Ribosomes / metabolism*

Substances

  • Escherichia coli Proteins
  • Molecular Chaperones
  • Protein Subunits
  • Proteins
  • trigger factor, E coli
  • Peptidylprolyl Isomerase

Associated data

  • PDB/1W26
  • PDB/1W2B