@article{9c664051dd7c423bb5207c0d7dee09d5,
title = "Structure and Function of Salmonella SifA Indicate that Its Interactions with SKIP, SseJ, and RhoA Family GTPases Induce Endosomal Tubulation",
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.",
keywords = "CELLBIO, MICROBIO, PROTEINS",
author = "Ohlson, {Maikke B.} and Zhiwei Huang and Alto, {Neal M.} and Blanc, {Marie Pierre} and Dixon, {Jack E.} and Jijie Chai and Miller, {Samuel I.}",
note = "Funding Information: We would like to thank Miller lab members Lisette Coye for the GFP-SifB plasmid and Richard Pfeutzner for SEC assistance. We thank Alex Merz (U. of Washington) and Maggie So (U. of Arizona) for graciously sharing and providing a link to their movie. We also thank the W.M. Keck Center for Advanced Studies in Neural Signaling for use of their DeltaVision microscope, and we express gratitude to J.H. Brumell (U. of Toronto) and S. Meresse (CNRS-INSERM-Universit{\'e} de la M{\'e}diterran{\'e}e) for sending plasmids. This work was supported by the Comprehensive Training in Inter-Disciplinary Oral Health Research T32 grant DE07132 (to M.B.O.), the Chinese Ministry of Science and Technology (to J.C.), and by the NIH/NIAID grants R01 AI048683 and U54 AI057141 for the Northwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research (S.I.M.). ",
year = "2008",
month = nov,
day = "13",
doi = "10.1016/j.chom.2008.08.012",
language = "English (US)",
volume = "4",
pages = "434--446",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "5",
}