PDBsum entry 1dpf

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protein ligands links
Gene regulation/signaling protein PDB id
Protein chain
178 a.a. *
Waters ×187
* Residue conservation analysis
PDB id:
Name: Gene regulation/signaling protein
Title: Crystal structure of a mg-free form of rhoa complexed with gdp
Structure: Rhoa. Chain: a. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
2.00Å     R-factor:   0.201     R-free:   0.252
Authors: T.Shimizu,K.Ihara,R.Maesaki,S.Kuroda,K.Kaibuchi,T.Hakoshima
Key ref:
T.Shimizu et al. (2000). An open conformation of switch I revealed by the crystal structure of a Mg2+-free form of RHOA complexed with GDP. Implications for the GDP/GTP exchange mechanism. J Biol Chem, 275, 18311-18317. PubMed id: 10748207 DOI: 10.1074/jbc.M910274199
27-Dec-99     Release date:   21-Jun-00    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P61586  (RHOA_HUMAN) -  Transforming protein RhoA
193 a.a.
178 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 5 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   19 terms 
  Biological process     viral reproduction   71 terms 
  Biochemical function     nucleotide binding     7 terms  


DOI no: 10.1074/jbc.M910274199 J Biol Chem 275:18311-18317 (2000)
PubMed id: 10748207  
An open conformation of switch I revealed by the crystal structure of a Mg2+-free form of RHOA complexed with GDP. Implications for the GDP/GTP exchange mechanism.
T.Shimizu, K.Ihara, R.Maesaki, S.Kuroda, K.Kaibuchi, T.Hakoshima.
Mg(2+) ions are essential for guanosine triphosphatase (GTPase) activity and play key roles in guanine nucleotide binding and preserving the structural integrity of GTP-binding proteins. We determined the crystal structure of a small GTPase RHOA complexed with GDP in the absence of Mg(2+) at 2.0-A resolution. Elimination of a Mg(2+) ion induces significant conformational changes in the switch I region that opens up the nucleotide-binding site. Similar structural changes have been observed in the switch regions of Ha-Ras bound to its guanine nucleotide exchange factor, Sos. This RHOA-GDP structure reveals an important regulatory role for Mg(2+) and suggests that guanine nucleotide exchange factor may utilize this feature of switch I to produce an open conformation in GDP/GTP exchange.
  Selected figure(s)  
Figure 5.
Fig. 5. A diagram showing the coordination of GDP in the RHOA Mg2+-free form. All dashed lines correspond to hydrogen bonding interactions (distance less than 3.5 Å), and the corresponding distances are indicated. The hydrogen bonds observed in the current structure but not in the GDP/Mg2+-bound form are highlighted in red.
Figure 6.
Fig. 6. Summary of contacts of the RHOA Mg2+-free form around the switch I region. Thin and thick dashed lines correspond to hydrogen bonding and van der Waals interactions, respectively.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2000, 275, 18311-18317) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20167596 J.H.Lebbink, A.Fish, A.Reumer, G.Natrajan, H.H.Winterwerp, and T.K.Sixma (2010).
Magnesium coordination controls the molecular switch function of DNA mismatch repair protein MutS.
  J Biol Chem, 285, 13131-13141.
PDB codes: 2wtu 3k0s
20236512 M.Della Peruta, C.Giagulli, C.Laudanna, A.Scarpa, and C.Sorio (2010).
RHOA and PRKCZ control different aspects of cell motility in pancreatic cancer metastatic clones.
  Mol Cancer, 9, 61.  
20131908 N.Nassar, K.Singh, and M.Garcia-Diaz (2010).
Structure of the dominant negative S17N mutant of Ras.
  Biochemistry, 49, 1970-1974.
PDB code: 3lo5
21031432 S.Rimmele, P.Gierschik, T.O.Joos, and N.Schneiderhan-Marra (2010).
Bead-based protein-protein interaction assays for the analysis of Rho GTPase signaling.
  J Mol Recognit, 23, 543-550.  
19782033 Y.Chen, Z.Yang, M.Meng, Y.Zhao, N.Dong, H.Yan, L.Liu, M.Ding, H.B.Peng, and F.Shao (2009).
Cullin mediates degradation of RhoA through evolutionarily conserved BTB adaptors to control actin cytoskeleton structure and cell movement.
  Mol Cell, 35, 841-855.  
18393397 M.Soundararajan, A.Turnbull, O.Fedorov, C.Johansson, and D.A.Doyle (2008).
RhoB can adopt a Mg2+ free conformation prior to GEF binding.
  Proteins, 72, 498-505.  
17218277 C.Thomas, I.Fricke, A.Scrima, A.Berken, and A.Wittinghofer (2007).
Structural evidence for a common intermediate in small G protein-GEF reactions.
  Mol Cell, 25, 141-149.
PDB codes: 2ntx 2nty
16857012 Y.W.Huang, M.C.Surka, D.Reynaud, C.Pace-Asciak, and W.S.Trimble (2006).
GTP binding and hydrolysis kinetics of human septin 2.
  FEBS J, 273, 3248-3260.  
15688002 K.L.Rossman, C.J.Der, and J.Sondek (2005).
GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors.
  Nat Rev Mol Cell Biol, 6, 167-180.  
15864301 R.Rose, M.Weyand, M.Lammers, T.Ishizaki, M.R.Ahmadian, and A.Wittinghofer (2005).
Structural and mechanistic insights into the interaction between Rho and mammalian Dia.
  Nature, 435, 513-518.
PDB code: 1z2c
14973186 J.Korlach, D.W.Baird, A.A.Heikal, K.R.Gee, G.R.Hoffman, and W.W.Webb (2004).
Spontaneous nucleotide exchange in low molecular weight GTPases by fluorescently labeled gamma-phosphate-linked GTP analogs.
  Proc Natl Acad Sci U S A, 101, 2800-2805.  
14576104 P.J.Budge, J.Lebowitz, and B.S.Graham (2003).
Antiviral activity of RhoA-derived peptides against respiratory syncytial virus is dependent on formation of peptide dimers.
  Antimicrob Agents Chemother, 47, 3470-3477.  
12093730 G.Buchwald, A.Friebel, J.E.Galán, W.D.Hardt, A.Wittinghofer, and K.Scheffzek (2002).
Structural basis for the reversible activation of a Rho protein by the bacterial toxin SopE.
  EMBO J, 21, 3286-3295.
PDB code: 1gzs
12009891 H.Garavini, K.Riento, J.P.Phelan, M.S.McAlister, A.J.Ridley, and N.H.Keep (2002).
Crystal structure of the core domain of RhoE/Rnd3: a constitutively activated small G protein.
  Biochemistry, 41, 6303-6310.
PDB code: 1gwn
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. Where a reference describes a PDB structure, the PDB codes are shown on the right.