Gene Symbol: spy
Description: periplasmic ATP-independent protein refolding chaperone, stress-induced
Alias: ECK1741, JW1732
Species: Escherichia coli str. K-12 substr. MG1655
Products:     spy

Top Publications

  1. Raivio T, Laird M, Joly J, Silhavy T. Tethering of CpxP to the inner membrane prevents spheroplast induction of the cpx envelope stress response. Mol Microbiol. 2000;37:1186-97 pubmed
    ..formation has previously been demonstrated to induce the expression of a periplasmic protein of unknown function, Spy. Analysis of spy expression in response to spheroplast formation by Western blot analysis and by lacZ operon fusion ..
  2. Raffa R, Raivio T. A third envelope stress signal transduction pathway in Escherichia coli. Mol Microbiol. 2002;45:1599-611 pubmed
    ..Previously, we identified the spy gene as a new Cpx regulon member of unknown function...
  3. DiGiuseppe P, Silhavy T. Signal detection and target gene induction by the CpxRA two-component system. J Bacteriol. 2003;185:2432-40 pubmed
    ..Finally, we show that two Cpx-regulated genes are differentially upregulated in response to different envelope stresses, suggesting the existence of three stress-responsive systems. ..
  4. Kwon E, Kim D, Gross C, Gross J, Kim K. The crystal structure Escherichia coli Spy. Protein Sci. 2010;19:2252-9 pubmed publisher
    ..Stress conditions such as spheroplast formation induce the expression of Spy via the Cpx or the Bae two-component systems in E. coli, though the function of Spy is unknown...
  5. Zoetendal E, Smith A, Sundset M, Mackie R. The BaeSR two-component regulatory system mediates resistance to condensed tannins in Escherichia coli. Appl Environ Microbiol. 2008;74:535-9 pubmed
    ..The cell envelope stress protein gene spy and the multidrug transporter-encoding operon mdtABCD, both under the control of the BaeSR two-component regulatory ..
  6. Noll M, Petrukhin K, Lutsenko S. Identification of a novel transcription regulator from Proteus mirabilis, PMTR, revealed a possible role of YJAI protein in balancing zinc in Escherichia coli. J Biol Chem. 1998;273:21393-401 pubmed
    ..We propose that YJAI is an important component of the zinc-balancing mechanism in E. coli, the up-regulation of which with PMTR results in an increased tolerance to zinc. ..
  7. Koldewey P, Stull F, Horowitz S, Martin R, Bardwell J. Forces Driving Chaperone Action. Cell. 2016;166:369-379 pubmed publisher
    ..that chaperones recognize unfolding intermediates by their hydrophobic nature, we discover that the model chaperone Spy uses long-range electrostatic interactions to rapidly bind to its unfolded client protein Im7...
  8. Horowitz S, Salmon L, Koldewey P, Ahlstrom L, Martin R, Quan S, et al. Visualizing chaperone-assisted protein folding. Nat Struct Mol Biol. 2016;23:691-7 pubmed publisher
    ..conformations of the substrate protein immunity protein 7 (Im7) in complex with the Escherichia coli chaperone Spy, and to capture a series of snapshots depicting the various folding states of Im7 bound to Spy...
  9. Quan S, Wang L, Petrotchenko E, Makepeace K, Horowitz S, Yang J, et al. Super Spy variants implicate flexibility in chaperone action. elife. 2014;3:e01584 pubmed publisher
    ..that links protein stability to antibiotic resistance to isolate variants of the newly discovered chaperone Spy that show an up to 7 fold improved chaperone activity against a variety of substrates...

More Information


  1. Quan S, Koldewey P, Tapley T, Kirsch N, Ruane K, Pfizenmaier J, et al. Genetic selection designed to stabilize proteins uncovers a chaperone called Spy. Nat Struct Mol Biol. 2011;18:262-9 pubmed publisher
    ..coli to stabilize a very unstable periplasmic protein, it massively overproduced a periplasmic protein called Spy, which increases the steady-state levels of a set of unstable protein mutants up to 700-fold...
  2. Garbe T, Kobayashi M, Yukawa H. Indole-inducible proteins in bacteria suggest membrane and oxidant toxicity. Arch Microbiol. 2000;173:78-82 pubmed
    ..A direct indication of membrane derangement in E. coli may be the indole-inducible overproduction of spheroplast protein y (Spy).
  3. Vertommen D, Depuydt M, Pan J, Leverrier P, Knoops L, Szikora J, et al. The disulphide isomerase DsbC cooperates with the oxidase DsbA in a DsbD-independent manner. Mol Microbiol. 2008;67:336-49 pubmed
    ..Our data indicate that DsbC can assist DsbA in a DsbD-independent manner to oxidatively fold envelope proteins. The view that DsbC's function is limited to the disulphide isomerization pathway should therefore be reinterpreted. ..
  4. Yamamoto K, Ogasawara H, Ishihama A. Involvement of multiple transcription factors for metal-induced spy gene expression in Escherichia coli. J Biotechnol. 2008;133:196-200 pubmed
    ..A periplasmic protein Spy of E. coli was found to be induced upon short-exposure to copper ion in CpxAR-dependent manner...
  5. Nishino K, Honda T, Yamaguchi A. Genome-wide analyses of Escherichia coli gene expression responsive to the BaeSR two-component regulatory system. J Bacteriol. 2005;187:1763-72 pubmed
    ..These data indicate that there is cross-regulation among the BaeSR, PhoBR, and CreBC two-component regulatory systems. Such a global analysis should reveal the regulatory network of the BaeSR system. ..
  6. Beloin C, Valle J, Latour Lambert P, Faure P, Kzreminski M, Balestrino D, et al. Global impact of mature biofilm lifestyle on Escherichia coli K-12 gene expression. Mol Microbiol. 2004;51:659-74 pubmed
    ..These results constitute a comprehensive analysis of the global transcriptional response triggered in mature E. coli biofilms and provide insights into its physiological signature. ..
  7. Stull F, Koldewey P, Humes J, Radford S, Bardwell J. Substrate protein folds while it is bound to the ATP-independent chaperone Spy. Nat Struct Mol Biol. 2016;23:53-58 pubmed publisher
    ..Here we characterized the kinetic mechanism of substrate folding by the small ATP-independent chaperone Spy from Escherichia coli...
  8. Hagenmaier S, Stierhof Y, Henning U. A new periplasmic protein of Escherichia coli which is synthesized in spheroplasts but not in intact cells. J Bacteriol. 1997;179:2073-6 pubmed
    The gene spy from Escherichia coli has been cloned and sequenced. It encodes a precursor of a so far unknown 139-residue, rather basic periplasmic protein...