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Chaperone release and unfolding of substrates in type III secretion

Nature volume 437, pages 911–915 (2005)Cite this article

Abstract

Type III protein secretion systems are essential virulence factors of many bacteria pathogenic to humans, animals and plants1. These systems mediate the transfer of bacterial virulence proteins directly into the host cell cytoplasm. Proteins are thought to travel this pathway in a largely unfolded manner, and a family of customized cytoplasmic chaperones, which specifically bind cognate secreted proteins, are essential for secretion. Here we show that InvC, an ATPase associated with a Salmonella enterica type III secretion system2, has a critical function in substrate recognition. Furthermore, InvC induces chaperone release from and unfolding of the cognate secreted protein in an ATP-dependent manner. Our results show a similarity between the mechanisms of substrate recognition by type III protein secretion systems and AAA + ATPase disassembly machines.

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Figure 1: The ATPase InvC interacts with TTS substrates.
Figure 2: InvC disassembles the chaperone/secreted protein complex.
Figure 3: InvC induces the unfolding of SptP.
Figure 4: Substrate unfolding is required for TTS.

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Acknowledgements

We thank A. Horwich and G. Farr for providing us with GroELD87K, S.-H. Lee for plasmid constructs, and members of the Galán laboratory for critical reading of the manuscript. This work was supported by a Public Health Service Grant.

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Authors and Affiliations

  1. Section of Microbial Pathogenesis, Yale University School of Medicine, Connecticut, 06536, New Haven, USA

    Yukihiro Akeda & Jorge E. Galán

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  1. Yukihiro Akeda
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  2. Jorge E. Galán
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Correspondence to Jorge E. Galán.

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Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

Supplementary information

Supplementary Figure 1

Demonstrates the unfolding of SptP after addition of InvC as assayed by gel filtration and transfer to a GroEL trap mutant. (PDF 75 kb)

Supplementary Figure Legend

Text to accompany the above Supplementary Figure (DOC 20 kb)

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Akeda, Y., Galán, J. Chaperone release and unfolding of substrates in type III secretion. Nature 437, 911–915 (2005). https://doi.org/10.1038/nature03992

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