PDBsum entry 2cjw

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protein ligands metals Protein-protein interface(s) links
G-protein PDB id
Protein chains
178 a.a. *
173 a.a. *
GDP ×2
_MG ×2
Waters ×127
* Residue conservation analysis
PDB id:
Name: G-protein
Title: Crystal structure of the small gtpase gem (gemdndcam) in complex to mg.Gdp
Structure: Gtp-binding protein gem. Chain: a. Fragment: g domain, residues 74-261. Synonym: gem, gtp-binding mitogen-induced t-cell protein, ras-like protein kir. Engineered: yes. Gtp-binding protein gem. Chain: b. Fragment: g domain, residues 74-261.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562
Biol. unit: Dimer (from PDB file)
2.10Å     R-factor:   0.212     R-free:   0.241
Authors: A.Splingard,J.Menetrey,M.Perderiset,J.Cicolari,F.Hamoudi, L.Cabanie,A.El Marjou,A.Wells,A.Houdusse,J.De Gunzburg
Key ref:
A.Splingard et al. (2007). Biochemical and structural characterization of the gem GTPase. J Biol Chem, 282, 1905-1915. PubMed id: 17107948 DOI: 10.1074/jbc.M604363200
09-Apr-06     Release date:   09-Nov-06    
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Protein chain
Pfam   ArchSchema ?
P55040  (GEM_HUMAN) -  GTP-binding protein GEM
296 a.a.
178 a.a.*
Protein chain
Pfam   ArchSchema ?
P55040  (GEM_HUMAN) -  GTP-binding protein GEM
296 a.a.
173 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 10 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   2 terms 
  Biological process     signal transduction   4 terms 
  Biochemical function     GTP binding     1 term  


DOI no: 10.1074/jbc.M604363200 J Biol Chem 282:1905-1915 (2007)
PubMed id: 17107948  
Biochemical and structural characterization of the gem GTPase.
A.Splingard, J.Ménétrey, M.Perderiset, J.Cicolari, K.Regazzoni, F.Hamoudi, L.Cabanié, A.El Marjou, A.Wells, A.Houdusse, Gunzburg.
RGK proteins, encompassing Rad, Gem, Rem1, and Rem2, constitute an intriguing branch of the Ras superfamily; their expression is regulated at the transcription level, they exhibit atypical nucleotide binding motifs, and they carry both large N- and C-terminal extensions. Biochemical and structural studies are required to better understand how such proteins function. Here, we report the first structure for a RGK protein: the crystal structure of a truncated form of the human Gem protein (G domain plus the first part of the C-terminal extension) in complex with Mg.GDP at 2.1 A resolution. It reveals that the G-domain fold and Mg.GDP binding site of Gem are similar to those found for other Ras family GTPases. The first part of the C-terminal extension adopts an alpha-helical conformation that extends along the alpha5 helix and interacts with the tip of the interswitch. Biochemical studies show that the affinities of Gem for GDP and GTP are considerably lower (micromolar range) compared with H-Ras, independent of the presence or absence of N- and C-terminal extensions, whereas its GTPase activity is higher than that of H-Ras and regulated by both extensions. We show how the bulky DXWEX motif, characteristic of the switch II of RGK proteins, affects the conformation of switch I and the phosphate-binding site. Altogether, our data reveal that Gem is a bona fide GTPase that exhibits striking structural and biochemical features that should impact its regulation and cellular activities.
  Selected figure(s)  
Figure 4.
Crystal structure of GDP-bound Gem-ΔNΔCaM. A, an overall view of Gem-ΔNΔCaM-GDP is shown with switch I in green, the interswitch in yellow, switch II in pink, and the C-terminal helix in blue. Note that both conformations of switch I and II are shown superposed in dark for molecule A and in bright for molecule B. B, the scheme of Mg·GDP interactions is given for molecule A with distances (see supplemental Table S1 for distances in molecule B). An inset of the magnesium coordination sphere is shown separately for clarity. C, close view of the C-terminal helix (blue) and its interaction with the interswitch (yellow) and the α5 helix (white) with secondary structure shown as coils. Hydrogen bonds are indicated by dashed lines. Note that for clarity, the orientation is not strictly conserved with the overall view (A). D, close view of the DMWEN motif in switch II (pink). The side chain of Glu^134 from molecule A is shown as transparent, indicating its partial occupancy. Orientation with the overall view is conserved.
Figure 5.
Comparison of the switch regions of GemΔNΔCaM-GDP with H-Ras-GDP/GTP. A, the H-Ras-GDP (Protein Data Bank code 4Q21; transparent light blue) and H-Ras-GTP (Protein Data Bank code 5P21; transparent dark blue) switch I-interswitch-switch II regions are shown superposed on the GemΔNΔCaM-GDP structure (same colors as in Fig. 4) for comparison. B, close view of A with overall structure shown as coils and the C-terminal part of switch II deleted for clarity. The first residues from the DMWEN and DTAGQ motifs in Gem and H-Ras, respectively, are shown in ball-and-stick representations for comparison. Note the divergent backbone trace and side chain directions between Gem and H-Ras after the Asp^131/Asp^57 residues and the position of Met^132 that shortens the β2 strand, pushing switch I away from the nucleotide binding site in Gem when compared with H-Ras.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2007, 282, 1905-1915) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20458179 C.Pang, S.M.Crump, L.Jin, R.N.Correll, B.S.Finlin, J.Satin, and D.A.Andres (2010).
Rem GTPase interacts with the proximal CaV1.2 C-terminus and modulates calcium-dependent channel inactivation.
  Channels (Austin), 4, 192-202.  
18164055 H.Schweikl, K.A.Hiller, A.Eckhardt, C.Bolay, G.Spagnuolo, T.Stempfl, and G.Schmalz (2008).
Differential gene expression involved in oxidative stress response caused by triethylene glycol dimethacrylate.
  Biomaterials, 29, 1377-1387.  
18042346 R.N.Correll, C.Pang, D.M.Niedowicz, B.S.Finlin, and D.A.Andres (2008).
The RGK family of GTP-binding proteins: regulators of voltage-dependent calcium channels and cytoskeleton remodeling.
  Cell Signal, 20, 292-300.  
17267693 A.Hatzoglou, I.Ader, A.Splingard, J.Flanders, E.Saade, I.Leroy, S.Traver, S.Aresta, and Gunzburg (2007).
Gem associates with Ezrin and acts via the Rho-GAP protein Gmip to down-regulate the Rho pathway.
  Mol Biol Cell, 18, 1242-1252.  
17605761 R.N.Mahalakshmi, K.Nagashima, M.Y.Ng, N.Inagaki, W.Hunziker, and P.Béguin (2007).
Nuclear transport of Kir/Gem requires specific signals and importin alpha5 and is regulated by calmodulin and predicted serine phosphorylations.
  Traffic, 8, 1150-1163.  
17605760 R.N.Mahalakshmi, M.Y.Ng, K.Guo, Z.Qi, W.Hunziker, and P.Béguin (2007).
Nuclear localization of endogenous RGK proteins and modulation of cell shape remodeling by regulated nuclear transport.
  Traffic, 8, 1164-1178.  
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.