Chaperone-Assisted Folding of Newly Synthesized Proteins in the Cytosol

Abstract

The way in which a newly synthesized polypeptide chain folds into its unique three-dimensional structure remains one of the fundamental questions in molecular biology. Protein folding in the cell is a problematic process and, in many cases, requires the assistance of a network of molecular chaperones to support productive protein folding in vivo. During protein biosynthesis, ribosome-associated chaperones guide the folding of the nascent polypeptide emerging from the ribosomal tunnel. In this review we summarize the basic principles of the protein-folding process and the involved chaperones, and focus on the role of ribosome-associated chaperones. Our discussion emphasizes the bacterial Trigger Factor, which is the best studied chaperone of this type. Recent advances have determined the atomic structure of the Trigger Factor, providing new, exciting insights into the role of ribosome-associated chaperones in co-translational protein folding.

Keywords:

• trigger factor
• GroEL
• DnaK
• nascent chains
• aggregation

Editor: Elizabeth A. Craig

We thank Drs. R. D. Wegrzyn, A. Erbse, and M. P. Mayer for comments on the manuscript and F. Merz for preparation of Figure 5. This work was supported by grants of the DFG to B. B. and E. D., a Heisenberg fellowship and the HFSP (Human Frontier Science Program) to E. D.