Research article summary (published 16 Sep 2009):

Detecting folding intermediates of a protein as it passes through the bacterial translocation channel.

Full Abstract

Most bacterial exported proteins cross the cytoplasmic membrane as unfolded polypeptides. However, little is known about how they fold during or after this process due to the difficulty in detecting folding intermediates. Here we identify cotranslational and posttranslational folding intermediates of a periplasmic protein in which the protein and DsbA, a periplasmic disulfide bond-forming enzyme, are covalently linked by a disulfide bond. The cotranslational mixed-disulfide intermediate is, upon further chain elongation, resolved, releasing the oxidized polypeptide, thus allowing us to follow the folding process. This analysis reveals that two cysteines that are joined to form a structural disulfide can play different roles during the folding reaction and that the mode of translocation (cotranslational verse posttranslational) can affect the folding process of a protein in the periplasm. The latter finding leads us to propose that the activity of the ribosome (translation) can modulate protein folding even in an extracytosolic compartment.

Author information

Author/s: Kadokura, Hiroshi (H); Beckwith, Jon (J);

Affiliation: Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA. hkadokura(-atsign-)bs.naist.jp

Grants: GM41883 (Agency:NIGMS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Cell (Cell), published in United States. (Language: eng)

Reference: 2009-Sep; vol 138 (issue 6) : pp 1164-73

Dates: Created 2009/09/21; Completed 2009/10/02;

PMID: 19766568, status: MEDLINE (last retrieval date: 10/2/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Alkaline Phosphatase - metabolism Cysteine - metabolism Escherichia coli - metabolism Escherichia coli Proteins - metabolism

Periplasm - metabolism Protein Biosynthesis Protein Disulfide-Isomerases - metabolism Protein Folding

Associated Chemicals: Escherichia coli Proteins (0) ; Cysteine (52-90-4) ; Alkaline Phosphatase (EC 3.1.3.1) ; phoA protein, E coli (EC 3.1.3.1) ; Protein Disulfide-Isomerases (EC 5.3.4.1) ; dsbA protein, E coli (EC 5.3.4.1)

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