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CHAPERONE‐ASSISTED PROTEIN FOLDING IN THE CYTOSOL
Author(s) -
Hartl F. Ulrich
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a153-b
Subject(s) - chaperone (clinical) , groel , chaperonin , co chaperone , protein folding , ribosome , microbiology and biotechnology , cytosol , folding (dsp implementation) , translation (biology) , chemistry , biology , biophysics , computational biology , biochemistry , hsp90 , heat shock protein , rna , messenger rna , escherichia coli , gene , medicine , engineering , pathology , electrical engineering , enzyme
The efficient folding of many newly‐synthesized proteins depends on assistance by molecular chaperones, which act to prevent protein misfolding and aggregation in the crowded environment of the cell. Nascent chain‐binding chaperones, including Trigger factor (TF) and Hsp70, stabilize elongating chains on ribosomes in a non‐aggregated state. Folding in the cytosol is achieved either on controlled chain release from these factors or following transfer of newly‐synthesized proteins to downstream chaperones, such as the cylindrical chaperonin complexes, GroEL and TRiC. The contribution of ribosome‐ and nascent chain‐binding chaperones to co‐ and post‐translational folding is not yet well understood. Recent evidence from our laboratory suggests that folding in the bacterial cytosol is geared towards a post‐translational mechanism, as a result of rapid translation speed and a delay in folding relative to translation caused by chaperones such as TF. In contrast, co‐translational and sequential domain folding are more efficiently supported by the eukaryotic translation‐chaperone machinery. We propose that this difference may have played a role in the explosive evolution of multi‐domain proteins in eukaryotes and can help explain why complex eukaryotic proteins often misfold and aggregate upon bacterial expression. Understanding the bacterial and eukaryotic translation‐folding machineries in more detail may provide the basis for engineering bacterial strains that are better adapted to the expression of eukaryotic proteins.