PDBsum entry 1rlf

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protein links
Signal transduction protein PDB id
Protein chain
90 a.a. *
* Residue conservation analysis
PDB id:
Name: Signal transduction protein
Title: Structure determination of the ras-binding domain of the ral-specific guanine nucleotide exchange factor rlf, nmr, 10 structures
Structure: Rlf. Chain: a. Fragment: ras binding domain, residues 646 - 735. Synonym: rlf-rbd. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 10 models
Authors: D.Esser,B.Bauer,R.M.F.Wolthuis,A.Wittinghofer,R.H.Cool,P.Bay
Key ref:
D.Esser et al. (1998). Structure determination of the Ras-binding domain of the Ral-specific guanine nucleotide exchange factor Rlf. Biochemistry, 37, 13453-13462. PubMed id: 9753431 DOI: 10.1021/bi9811664
09-Jul-98     Release date:   16-Feb-99    
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Protein chain
Pfam   ArchSchema ?
Q61193  (RGL2_MOUSE) -  Ral guanine nucleotide dissociation stimulator-like 2
778 a.a.
90 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     signal transduction   1 term 


DOI no: 10.1021/bi9811664 Biochemistry 37:13453-13462 (1998)
PubMed id: 9753431  
Structure determination of the Ras-binding domain of the Ral-specific guanine nucleotide exchange factor Rlf.
D.Esser, B.Bauer, R.M.Wolthuis, A.Wittinghofer, R.H.Cool, P.Bayer.
Ral-specific guanine nucleotide exchange factors RalGDS, Rgl, and Rlf have been suggested to function as intermediates between Ras and Ral pathways by being able to bind Ras proteins through their C-terminal Ras-binding domains (RBD). The RBDs of RalGDS and of the Ser/Thr kinase c-Raf-1 have been shown to have the same tertiary structure. In contrast to the RBDs of Raf and RalGDS, which bind either Ras or Rap with high affinity, Rlf-RBD has a similar affinity for both GTP-binding proteins. To be able to compare these RBDs on a structural level, we have solved the three-dimensional structure of Rlf-RBD by NMR spectroscopy. The overall tertiary structure of Rlf-RBD shows the betabetaalphabetabetaalphabeta-fold of the ubiquitin superfamily and is very similar to that of RalGDS-RBD. The binding interface of Rlf-RBD to Ras was mapped using chemical shift analysis and indicated a binding mode similar to that in the case of Rap.Raf-RBD. However, comparison of the putatively interacting regions revealed structural differences which are proposed to be responsible for the different substrate affinities of Rlf-, RalGDS-, and Raf-RBD.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20617134 S.Jancík, J.Drábek, D.Radzioch, and M.Hajdúch (2010).
Clinical relevance of KRAS in human cancers.
  J Biomed Biotechnol, 2010, 150960.  
  20178605 V.González-Pérez, D.J.Reiner, J.K.Alan, C.Mitchell, L.J.Edwards, V.Khazak, C.J.Der, and A.D.Cox (2010).
Genetic and functional characterization of putative Ras/Raf interaction inhibitors in C. elegans and mammalian cells.
  J Mol Signal, 5, 2.  
16928684 M.Kukimoto-Niino, T.Takagi, R.Akasaka, K.Murayama, T.Uchikubo-Kamo, T.Terada, M.Inoue, S.Watanabe, A.Tanaka, Y.Hayashizaki, T.Kigawa, M.Shirouzu, and S.Yokoyama (2006).
Crystal structure of the RUN domain of the RAP2-interacting protein x.
  J Biol Chem, 281, 31843-31853.
PDB codes: 2cxf 2cxl 2dwg 2dwk
15653425 E.J.Helmreich (2004).
Structural flexibility of small GTPases. Can it explain their functional versatility?
  Biol Chem, 385, 1121-1136.  
12581669 C.Herrmann (2003).
Ras-effector interactions: after one decade.
  Curr Opin Struct Biol, 13, 122-129.  
12091396 L.Liu, B.R.Schwartz, J.Tupper, N.Lin, R.K.Winn, and J.M.Harlan (2002).
The GTPase Rap1 regulates phorbol 12-myristate 13-acetate-stimulated but not ligand-induced beta 1 integrin-dependent leukocyte adhesion.
  J Biol Chem, 277, 40893-40900.  
12183360 N.M.Hamad, J.H.Elconin, A.E.Karnoub, W.Bai, J.N.Rich, R.T.Abraham, C.J.Der, and C.M.Counter (2002).
Distinct requirements for Ras oncogenesis in human versus mouse cells.
  Genes Dev, 16, 2045-2057.  
11709168 K.Scheffzek, P.Grünewald, S.Wohlgemuth, W.Kabsch, H.Tu, M.Wigler, A.Wittinghofer, and C.Herrmann (2001).
The Ras-Byr2RBD complex: structural basis for Ras effector recognition in yeast.
  Structure, 9, 1043-1050.
PDB code: 1k8r
11369865 W.Gronwald, E.Brunner, F.Huber, M.Wenzler, C.Herrmann, and H.R.Kalbitzer (2001).
Overcoming the problems associated with poor spectra quality of the protein kinase Byr2 using residual dipolar couplings.
  Protein Sci, 10, 1260-1263.  
11709167 W.Gronwald, F.Huber, P.Grünewald, M.Spörner, S.Wohlgemuth, C.Herrmann, and H.R.Kalbitzer (2001).
Solution structure of the Ras binding domain of the protein kinase Byr2 from Schizosaccharomyces pombe.
  Structure, 9, 1029-1041.
PDB code: 1i35
10364219 B.Bauer, G.Mirey, I.R.Vetter, J.A.García-Ranea, A.Valencia, A.Wittinghofer, J.H.Camonis, and R.H.Cool (1999).
Effector recognition by the small GTP-binding proteins Ras and Ral.
  J Biol Chem, 274, 17763-17770.  
  10454576 R.H.Cool, G.Schmidt, C.U.Lenzen, H.Prinz, D.Vogt, and A.Wittinghofer (1999).
The Ras mutant D119N is both dominant negative and activated.
  Mol Cell Biol, 19, 6297-6305.  
10072355 R.M.Wolthuis, and J.L.Bos (1999).
Ras caught in another affair: the exchange factors for Ral.
  Curr Opin Genet Dev, 9, 112-117.  
10085114 V.Nancy, R.M.Wolthuis, Tand, I.Janoueix-Lerosey, J.L.Bos, and Gunzburg (1999).
Identification and characterization of potential effector molecules of the Ras-related GTPase Rap2.
  J Biol Chem, 274, 8737-8745.  
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