Structural and functional studies on the interaction of gspc and gspd in the type ii secretion system

Konstantin V. Korotkov, Tanya L. Johnson, Michael G. Jobling, Jonathan Pruneda, Els Pardon, Annie Héroux, Stewart Turley, Jan Steyaert, Randall K. Holmes, Maria Sandkvist, Wim G.J. Hol

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Type II secretion systems (T2SSs) are critical for secretion of many proteins from Gram-negative bacteria. In the T2SS, the outer membrane secretin GspD forms a multimeric pore for translocation of secreted proteins. GspD and the inner membrane protein GspC interact with each other via periplasmic domains. Three different crystal structures of the homology region domain of GspC (GspC HR) in complex with either two or three domains of the N-terminal region of GspD from enterotoxigenic Escherichia coli show that GspC HR adopts an all-β topology. N-terminal β-strands of GspC and the N0 domain of GspD are major components of the interface between these inner and outer membrane proteins from the T2SS. The biological relevance of the observed GspC-GspD interface is shown by analysis of variant proteins in two-hybrid studies and by the effect of mutations in homologous genes on extracellular secretion and subcellular distribution of GspC in Vibrio cholerae. Substitutions of interface residues of GspD have a dramatic effect on the focal distribution of GspC in V. cholerae. These studies indicate that the GspC HR-GspD N0 interactions observed in the crystal structure are essential for T2SS function. Possible implications of our structures for the stoichiometry of the T2SS and exoprotein secretion are discussed.

Original languageEnglish (US)
Article numbere1002228
JournalPLoS Pathogens
Volume7
Issue number9
DOIs
StatePublished - Sep 1 2011
Externally publishedYes

Fingerprint

Vibrio cholerae
Membrane Proteins
Enterotoxigenic Escherichia coli
Secretin
Protein Transport
Gram-Negative Bacteria
Proteins
Mutation
Membranes
Genes
Type II Secretion Systems

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Korotkov, K. V., Johnson, T. L., Jobling, M. G., Pruneda, J., Pardon, E., Héroux, A., ... Hol, W. G. J. (2011). Structural and functional studies on the interaction of gspc and gspd in the type ii secretion system. PLoS Pathogens, 7(9), [e1002228]. https://doi.org/10.1371/journal.ppat.1002228

Structural and functional studies on the interaction of gspc and gspd in the type ii secretion system. / Korotkov, Konstantin V.; Johnson, Tanya L.; Jobling, Michael G.; Pruneda, Jonathan; Pardon, Els; Héroux, Annie; Turley, Stewart; Steyaert, Jan; Holmes, Randall K.; Sandkvist, Maria; Hol, Wim G.J.

In: PLoS Pathogens, Vol. 7, No. 9, e1002228, 01.09.2011.

Research output: Contribution to journalArticle

Korotkov, KV, Johnson, TL, Jobling, MG, Pruneda, J, Pardon, E, Héroux, A, Turley, S, Steyaert, J, Holmes, RK, Sandkvist, M & Hol, WGJ 2011, 'Structural and functional studies on the interaction of gspc and gspd in the type ii secretion system', PLoS Pathogens, vol. 7, no. 9, e1002228. https://doi.org/10.1371/journal.ppat.1002228
Korotkov, Konstantin V. ; Johnson, Tanya L. ; Jobling, Michael G. ; Pruneda, Jonathan ; Pardon, Els ; Héroux, Annie ; Turley, Stewart ; Steyaert, Jan ; Holmes, Randall K. ; Sandkvist, Maria ; Hol, Wim G.J. / Structural and functional studies on the interaction of gspc and gspd in the type ii secretion system. In: PLoS Pathogens. 2011 ; Vol. 7, No. 9.
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