Structural highlights
1gzs is a 4 chain structure with sequence from [1] and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | |
| Related: | 1a4r, 1aje, 1an0, 1cee, 1cf4, 1doa, 1e0a, 1ees, 1grn, 1ki1, 1kz7, 1kzg, 2ngr |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum |
Function
[SOPE_SALTM] Activator for both CDC42 and RAC1 by directly engaging these Rho GTPases and acting as potent guanine nucleotide exchange factor (GEF). This activation results in actin cytoskeleton rearrangements and stimulates membrane ruffling, promoting bacterial entry into non-phagocytic cells. Also activates MAPK8, indicating that it is capable of stimulating signaling pathways that can lead to nuclear responses. Chaperone InvB is required for secretion and translocation of SopE.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The bacterial enteropathogen Salmonella typhimurium employs a type III secretion system to inject bacterial toxins into the host cell cytosol. These toxins transiently activate Rho family GTP-binding protein-dependent signaling cascades to induce cytoskeletal rearrangements. One of these translocated Salmonella toxins, SopE, can activate Cdc42 in a Dbl-like fashion despite its lack of sequence similarity to Dbl-like proteins, the Rho-specific eukaryotic guanine nucleotide exchange factors. To elucidate the mechanism of SopE-mediated guanine nucleotide exchange, we have analyzed the structure of the complex between a catalytic fragment of SopE and Cdc42. SopE binds to and locks the switch I and switch II regions of Cdc42 in a conformation that promotes guanine nucleotide release. This conformation is strikingly similar to that of Rac1 in complex with the eukaryotic Dbl-like exchange factor Tiam1. However, the catalytic domain of SopE has an entirely different architecture from that of Tiam1 and interacts with the switch regions via different amino acids. Therefore, SopE represents the first example of a non-Dbl-like protein capable of inducing guanine nucleotide exchange in Rho family proteins.
Structural basis for the reversible activation of a Rho protein by the bacterial toxin SopE.,Buchwald G, Friebel A, Galan JE, Hardt WD, Wittinghofer A, Scheffzek K EMBO J. 2002 Jul 1;21(13):3286-95. PMID:12093730[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Friebel A, Ilchmann H, Aepfelbacher M, Ehrbar K, Machleidt W, Hardt WD. SopE and SopE2 from Salmonella typhimurium activate different sets of RhoGTPases of the host cell. J Biol Chem. 2001 Sep 7;276(36):34035-40. Epub 2001 Jul 5. PMID:11440999 doi:http://dx.doi.org/10.1074/jbc.M100609200
- ↑ Hardt WD, Chen LM, Schuebel KE, Bustelo XR, Galan JE. S. typhimurium encodes an activator of Rho GTPases that induces membrane ruffling and nuclear responses in host cells. Cell. 1998 May 29;93(5):815-26. PMID:9630225
- ↑ Buchwald G, Friebel A, Galan JE, Hardt WD, Wittinghofer A, Scheffzek K. Structural basis for the reversible activation of a Rho protein by the bacterial toxin SopE. EMBO J. 2002 Jul 1;21(13):3286-95. PMID:12093730 doi:10.1093/emboj/cdf329
