Structure and Function of Salmonella SifA Indicate that Its Interactions with SKIP, SseJ, and RhoA Family GTPases Induce Endosomal Tubulation

Maikke B. Ohlson, Zhiwei Huang, Neal M. Alto, Marie Pierre Blanc, Jack E. Dixon, Jijie Chai, Samuel I. Miller

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

The Salmonella typhimurium type III secretion effector protein SifA is essential for inducing tubulation of the Salmonella phagosome and binds the mammalian kinesin-binding protein SKIP. Coexpression of SifA with the effector SseJ induced tubulation of mammalian cell endosomes, similar to that induced by Salmonella infection. Interestingly, GTP-bound RhoA, RhoB, and RhoC also induced endosomal tubulation when coexpressed with SseJ, indicating that SifA likely mimics or activates a RhoA family GTPase. The structure of SifA in complex with the PH domain of SKIP revealed that SifA has two distinct domains; the amino terminus binds SKIP, and the carboxyl terminus has a fold similar to SopE, a Salmonella effector with Rho GTPase guanine nucleotide exchange factor activity (GEF). Similar to GEFs, SifA interacted with GDP-bound RhoA, and purified SseJ and RhoA formed a protein complex, suggesting that SifA, SKIP, SseJ, and RhoA family GTPases cooperatively promote host membrane tubulation.

Original languageEnglish (US)
Pages (from-to)434-446
Number of pages13
JournalCell Host and Microbe
Volume4
Issue number5
DOIs
StatePublished - Nov 13 2008

Fingerprint

GTP Phosphohydrolases
Salmonella
Rho Guanine Nucleotide Exchange Factors
Kinesin
Phagosomes
rho GTP-Binding Proteins
Salmonella Infections
Endosomes
Salmonella typhimurium
Guanosine Triphosphate
Carrier Proteins
Proteins
Membranes
Pleckstrin Homology Domains

Keywords

  • CELLBIO
  • MICROBIO
  • PROTEINS

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

Cite this

Structure and Function of Salmonella SifA Indicate that Its Interactions with SKIP, SseJ, and RhoA Family GTPases Induce Endosomal Tubulation. / Ohlson, Maikke B.; Huang, Zhiwei; Alto, Neal M.; Blanc, Marie Pierre; Dixon, Jack E.; Chai, Jijie; Miller, Samuel I.

In: Cell Host and Microbe, Vol. 4, No. 5, 13.11.2008, p. 434-446.

Research output: Contribution to journalArticle

Ohlson, Maikke B. ; Huang, Zhiwei ; Alto, Neal M. ; Blanc, Marie Pierre ; Dixon, Jack E. ; Chai, Jijie ; Miller, Samuel I. / Structure and Function of Salmonella SifA Indicate that Its Interactions with SKIP, SseJ, and RhoA Family GTPases Induce Endosomal Tubulation. In: Cell Host and Microbe. 2008 ; Vol. 4, No. 5. pp. 434-446.
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AU - Miller, Samuel I.

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