@article{4ee935a21e1c4eab9cc003a25f3565a6,
title = "Structural insights into host GTPase isoform selection by a family of bacterial GEF mimics",
abstract = "The Escherichia coli type III effector Map belongs to a large family of bacterial virulence factors that activate host Rho GTPase signaling pathways through an unknown molecular mechanism. Here we report direct evidence that Map functions as a potent and selective guanine-nucleotide exchange factor (GEF) for Cdc42. The 2.3-{\AA} structure of the Map-Cdc42 complex revealed that Map mimics the GEF strategy of the mammalian Dbl family but has a three-dimensional architecture that is nearly identical to the bacterial GEF Salmonella spp. SopE. A comparative analysis between human and bacterial GEFs revealed a previously uncharacterized pairing mechanism between Map and the variable β2-3 interswitch region of Cdc42. We propose a GTPase selection model that is experimentally validated by the preferential activation Rac1 and RhoA by the Shigella spp. effectors IpgB1 and IpgB2, respectively. These results significantly expand the repertoire of bacterial GEF mimics and unify a GEF selection mechanism for host GTPase substrates.",
author = "Zhiwei Huang and Sutton, {Sarah E.} and Wallenfang, {Adam J.} and Orchard, {Robert C.} and Xiaojing Wu and Yingcai Feng and Jijie Chai and Alto, {Neal M.}",
note = "Funding Information: N.M.A.). This work was supported by the Rita C. and William P. Clements Jr. endowment for scholars program (UTSW Medical Center) and by the Texas ARP grant 010019-0085-29007 to N.M.A., and by the Chinese Ministry of Science and Technology {\textquoteleft}{\textquoteleft}863{\textquoteright}{\textquoteright} grant no. 2008AA022305 and {\textquoteleft}{\textquoteleft}973{\textquoteright}{\textquoteright} grant no. 2006CB806704 to J.C. Funding Information: We would like to specifically thank J. Dixon (University of California, San Diego), M. Rosen and Kim Orth (University of Texas, Southwestern (UTSW)) for helpful discussion in preparation of this manuscript and for providing valuable reagents, and B. Kenny (Institute for Cell and Molecular Biosciences, Medical School, University of Newcastle) for wild-type EPEC2348/69 and EPECDmap strains. S.E.S. and A.J.W. are supported by Texas ARP (grant 010019-0085-29007 to N.M.A.) and R.C.O is supported by the Welch foundation (grant I-1704 to",
year = "2009",
month = aug,
doi = "10.1038/nsmb.1647",
language = "English (US)",
volume = "16",
pages = "853--860",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "Nature Publishing Group",
number = "8",
}