PDBsum entry 2a9k

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protein ligands metals Protein-protein interface(s) links
Protein binding/transferase PDB id
Protein chains
170 a.a. *
207 a.a. *
Waters ×210
* Residue conservation analysis
PDB id:
Name: Protein binding/transferase
Title: Crystal structure of the c3bot-NAD-rala complex reveals a no of action of a bacterial exoenzyme
Structure: Ras-related protein ral-a. Chain: a. Engineered: yes. Mono-adp-ribosyltransferase c3. Chain: b. Synonym: exoenzyme c3. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: rala, ral. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Clostridium botulinum d phage. Organism_taxid: 29342. Gene: c3.
Biol. unit: Dimer (from PQS)
1.73Å     R-factor:   0.188     R-free:   0.225
Authors: A.Pautsch,M.Vogelsgesang,J.Trankle,C.Herrmann,K.Aktories
Key ref:
A.Pautsch et al. (2005). Crystal structure of the C3bot-RalA complex reveals a novel type of action of a bacterial exoenzyme. EMBO J, 24, 3670-3680. PubMed id: 16177825 DOI: 10.1038/sj.emboj.7600813
12-Jul-05     Release date:   11-Oct-05    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P11233  (RALA_HUMAN) -  Ras-related protein Ral-A
206 a.a.
170 a.a.
Protein chain
Pfam   ArchSchema ?
P15879  (ARC3_CBDP) -  Mono-ADP-ribosyltransferase C3
251 a.a.
207 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   4 terms 
  Biological process     viral reproduction   7 terms 
  Biochemical function     transferase activity     5 terms  


DOI no: 10.1038/sj.emboj.7600813 EMBO J 24:3670-3680 (2005)
PubMed id: 16177825  
Crystal structure of the C3bot-RalA complex reveals a novel type of action of a bacterial exoenzyme.
A.Pautsch, M.Vogelsgesang, J.Tränkle, C.Herrmann, K.Aktories.
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.
  Selected figure(s)  
Figure 2.
Figure 2 Structure of the RalA-GDP-C3bot complex. Ribbon diagram of RalA (grey) and C3bot (cyan) as a stereo view. The RalA switch-I and -II regions are coloured blue and red, respectively. The P loop is shown in green. The bound GDP molecule is shown as a stick model coloured by atom type (C, yellow; O, red; N, blue; P, magenta) and the Mg2+ ion as a black sphere. Helices 2 and 3 of RalA are labelled as a2 and a3, respectively. The catalytic ARTT loop of C3bot is shown in yellow. The secondary structure elements 3, 4, 6 and 7 of C3bot are labelled a'3, a'4, b'6 and b'7, respectively.
Figure 5.
Figure 5 The binding site of RalA and the putative Rho-binding site of C3 proteins. C3bot is shown as a grey surface representation with three regions, which are important for substrate recognition in the related transferases ExoS and ExoT (see text) shown in cyan. RalA is shown as a ribbon representation in magenta. GDP and NAD are shown as stick models coloured by atom type as in Figure 2. The boxed region is shown as a close-up with RalA as a space-filling model. Labelled residues of C3bot are marked by a dash.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: EMBO J (2005, 24, 3670-3680) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19840027 J.Fahrer, J.Kuban, K.Heine, G.Rupps, E.Kaiser, E.Felder, R.Benz, and H.Barth (2010).
Selective and specific internalization of clostridial C3 ADP-ribosyltransferases into macrophages and monocytes.
  Cell Microbiol, 12, 233-247.  
21170356 R.J.Fieldhouse, Z.Turgeon, D.White, and A.R.Merrill (2010).
Cholera- and anthrax-like toxins are among several new ADP-ribosyltransferases.
  PLoS Comput Biol, 6, e1001029.  
19824793 M.R.Popoff, and P.Bouvet (2009).
Clostridial toxins.
  Future Microbiol, 4, 1021-1064.  
18227351 Gorter, R.M.Reijmers, E.A.Beuling, H.P.Naber, A.Kuil, M.J.Kersten, S.T.Pals, and M.Spaargaren (2008).
The small GTPase Ral mediates SDF-1-induced migration of B cells and multiple myeloma cells.
  Blood, 111, 3364-3372.  
17146673 M.Vogelsgesang, A.Pautsch, and K.Aktories (2007).
C3 exoenzymes, novel insights into structure and action of Rho-ADP-ribosylating toxins.
  Naunyn Schmiedebergs Arch Pharmacol, 374, 347-360.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.