| Structural highlights
2a9k is a 2 chain structure with sequence from Bacteriophage c3 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , |
| Related: | 2a78, 1u8z, 1u90, 1uad, 2bov, 1g24 |
| Gene: | RALA, RAL (HUMAN), C3 (Bacteriophage C3) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum |
Function
[RALA_HUMAN] Multifunctional GTPase involved in a variety of cellular processes including gene expression, cell migration, cell proliferation, oncogenic transformation and membrane trafficking. Accomplishes its multiple functions by interacting with distinct downstream effectors. Acts as a GTP sensor for GTP-dependent exocytosis of dense core vesicles. Plays a role in the early stages of cytokinesis and is required to tether the exocyst to the cytokinetic furrow. The RALA-exocyst complex regulates integrin-dependent membrane raft exocytosis and growth signaling. Key regulator of LPAR1 signaling and competes with ADRBK1 for binding to LPAR1 thus affecting the signaling properties of the receptor. Required for anchorage-independent proliferation of transformed cells.[1] [2] [3] [ARC3_CBDP] ADP-ribosylates eukaryotic Rho and Rac proteins on an asparagine residue.
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
C3 exoenzymes from bacterial pathogens ADP-ribosylate and inactivate low-molecular-mass GTPases of the Rho subfamily. Ral, a Ras subfamily GTPase, binds the C3 exoenzymes from Clostridium botulinum and C. limosum with high affinity without being a substrate for ADP ribosylation. In the complex, the ADP-ribosyltransferase activity of C3 is blocked, while binding of NAD and NAD-glycohydrolase activity remain. Here we report the crystal structure of C3 from C. botulinum in a complex with GDP-bound RalA at 1.8 A resolution. C3 binds RalA with a helix-loop-helix motif that is adjacent to the active site. A quaternary complex with NAD suggests a mode for ADP-ribosyltransferase inhibition. Interaction of C3 with RalA occurs at a unique interface formed by the switch-II region, helix alpha3 and the P loop of the GTPase. C3-binding stabilizes the GDP-bound conformation of RalA and blocks nucleotide release. Our data indicate that C. botulinum exoenzyme C3 is a single-domain toxin with bifunctional properties targeting Rho GTPases by ADP ribosylation and Ral by a guanine nucleotide dissociation inhibitor-like effect, which blocks nucleotide exchange.
Crystal structure of the C3bot-RalA complex reveals a novel type of action of a bacterial exoenzyme.,Pautsch A, Vogelsgesang M, Trankle J, Herrmann C, Aktories K EMBO J. 2005 Oct 19;24(20):3670-80. Epub 2005 Sep 22. PMID:16177825[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Cascone I, Selimoglu R, Ozdemir C, Del Nery E, Yeaman C, White M, Camonis J. Distinct roles of RalA and RalB in the progression of cytokinesis are supported by distinct RalGEFs. EMBO J. 2008 Sep 17;27(18):2375-87. doi: 10.1038/emboj.2008.166. Epub 2008 Aug, 28. PMID:18756269 doi:http://dx.doi.org/10.1038/emboj.2008.166
- ↑ Aziziyeh AI, Li TT, Pape C, Pampillo M, Chidiac P, Possmayer F, Babwah AV, Bhattacharya M. Dual regulation of lysophosphatidic acid (LPA1) receptor signalling by Ral and GRK. Cell Signal. 2009 Jul;21(7):1207-17. doi: 10.1016/j.cellsig.2009.03.011. Epub, 2009 Mar 21. PMID:19306925 doi:10.1016/j.cellsig.2009.03.011
- ↑ Balasubramanian N, Meier JA, Scott DW, Norambuena A, White MA, Schwartz MA. RalA-exocyst complex regulates integrin-dependent membrane raft exocytosis and growth signaling. Curr Biol. 2010 Jan 12;20(1):75-9. doi: 10.1016/j.cub.2009.11.016. Epub 2009 Dec , 10. PMID:20005108 doi:http://dx.doi.org/10.1016/j.cub.2009.11.016
- ↑ Pautsch A, Vogelsgesang M, Trankle J, Herrmann C, Aktories K. Crystal structure of the C3bot-RalA complex reveals a novel type of action of a bacterial exoenzyme. EMBO J. 2005 Oct 19;24(20):3670-80. Epub 2005 Sep 22. PMID:16177825
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