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PDBsum entry 1lfd

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protein ligands metals Protein-protein interface(s) links
Complex (ralgds/ras) PDB id
1lfd
Jmol
Contents
Protein chains
87 a.a. *
167 a.a. *
Ligands
GNP ×2
Metals
_MG ×2
Waters ×292
* Residue conservation analysis
PDB id:
1lfd
Name: Complex (ralgds/ras)
Title: Crystal structure of the active ras protein complexed with the ras-interacting domain of ralgds
Structure: Ralgds. Chain: a, c. Fragment: ras-interacting domain, c-terminal domain. Engineered: yes. Other_details: binds to active human ras. Ras. Chain: b, d. Fragment: residues 1-171. Engineered: yes.
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: human ras. Expressed in: escherichia coli. Expression_system_taxid: 562. (Residues 767-864) fused to gst protein. Homo sapiens. Human.
Biol. unit: Dimer (from PQS)
Resolution:
2.10Å     R-factor:   0.206     R-free:   0.282
Authors: L.Huang,F.Hofer,G.S.Martin,S.-H.Kim
Key ref: L.Huang et al. (1998). Structural basis for the interaction of Ras with RalGDS. Nat Struct Biol, 5, 422-426. PubMed id: 9628477
Date:
29-Apr-98     Release date:   04-May-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q03386  (GNDS_RAT) -  Ral guanine nucleotide dissociation stimulator
Seq:
Struc:
 
Seq:
Struc:
895 a.a.
87 a.a.
Protein chains
Pfam   ArchSchema ?
P01112  (RASH_HUMAN) -  GTPase HRas
Seq:
Struc:
189 a.a.
167 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biological process     signal transduction   3 terms 
  Biochemical function     GTP binding     1 term  

 

 
Nat Struct Biol 5:422-426 (1998)
PubMed id: 9628477  
 
 
Structural basis for the interaction of Ras with RalGDS.
L.Huang, F.Hofer, G.S.Martin, S.H.Kim.
 
  ABSTRACT  
 
The Ras protein signals to a number of distinct pathways by interacting with diverse downstream effectors. Among the effectors of Ras are the Raf kinase and RalGDS, a guanine nucleotide dissociation stimulator specific for Ral. Despite the absence of significant sequence similarities, both effectors bind directly to Ras, but with different specificities. We report here the 2.1 A crystal structure of the complex between Ras and the Ras-interacting domain (RID) of RalGDS. This structure reveals that the beta-sheet of the RID joins the switch I region of Ras to form an extended beta-sheet with a topology similar to that found in the Rap-Raf complex. However, the side chain interactions at the joining junctions of the two interacting systems and the relative orientation of the two binding domains are distinctly different. Furthermore, in the case of the Ras-RID complex a second RID molecule also interacts with a different part of the Ras molecule, the switch II region. These findings account for the cross-talk between the Ras and Ral pathways and the specificity with which Ras distinguishes the two effectors.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20949621 L.Gremer, T.Merbitz-Zahradnik, R.Dvorsky, I.C.Cirstea, C.P.Kratz, M.Zenker, A.Wittinghofer, and M.R.Ahmadian (2011).
Germline KRAS mutations cause aberrant biochemical and physical properties leading to developmental disorders.
  Hum Mutat, 32, 33-43.  
20150896 B.T.Goult, M.Bouaouina, P.R.Elliott, N.Bate, B.Patel, A.R.Gingras, J.G.Grossmann, G.C.Roberts, D.A.Calderwood, D.R.Critchley, and I.L.Barsukov (2010).
Structure of a double ubiquitin-like domain in the talin head: a role in integrin activation.
  EMBO J, 29, 1069-1080.
PDB codes: 2kc1 2kc2 2kma
19776012 C.Kiel, D.Filchtinski, M.Spoerner, G.Schreiber, H.R.Kalbitzer, and C.Herrmann (2009).
Improved binding of raf to Ras.GDP is correlated with biological activity.
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19654617 D.F.Ceccarelli, and F.Sicheri (2009).
Grb-ing hold of insulin signaling.
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19801192 G.Fuentes, and A.Valencia (2009).
Ras classical effectors: new tales from in silico complexes.
  Trends Biochem Sci, 34, 533-539.  
19648926 R.S.Depetris, J.Wu, and S.R.Hubbard (2009).
Structural and functional studies of the Ras-associating and pleckstrin-homology domains of Grb10 and Grb14.
  Nat Struct Mol Biol, 16, 833-839.
PDB code: 3hk0
18786395 A.Schulte, B.Stolp, A.Schönichen, O.Pylypenko, A.Rak, O.T.Fackler, and M.Geyer (2008).
The human formin FHOD1 contains a bipartite structure of FH3 and GTPase-binding domains required for activation.
  Structure, 16, 1313-1323.
PDB code: 3dad
19096503 C.Kiel, D.Aydin, and L.Serrano (2008).
Association rate constants of ras-effector interactions are evolutionarily conserved.
  PLoS Comput Biol, 4, e1000245.  
18186463 D.Motiejunas, R.Gabdoulline, T.Wang, A.Feldman-Salit, T.Johann, P.J.Winn, and R.C.Wade (2008).
Protein-protein docking by simulating the process of association subject to biochemical constraints.
  Proteins, 71, 1955-1969.  
18354782 L.E.Goldfinger (2008).
Choose your own path: specificity in Ras GTPase signaling.
  Mol Biosyst, 4, 293-299.  
18275816 Y.Tong, P.K.Hota, M.B.Hamaneh, and M.Buck (2008).
Insights into oncogenic mutations of plexin-B1 based on the solution structure of the Rho GTPase binding domain.
  Structure, 16, 246-258.
PDB code: 2jph
17605815 A.M.Burroughs, S.Balaji, L.M.Iyer, and L.Aravind (2007).
Small but versatile: the extraordinary functional and structural diversity of the beta-grasp fold.
  Biol Direct, 2, 18.  
17599936 C.Kiel, and L.Serrano (2007).
Prediction of Ras-effector interactions using position energy matrices.
  Bioinformatics, 23, 2226-2230.  
17728234 P.Serrano, M.A.Johnson, M.S.Almeida, R.Horst, T.Herrmann, J.S.Joseph, B.W.Neuman, V.Subramanian, K.S.Saikatendu, M.J.Buchmeier, R.C.Stevens, P.Kuhn, and K.Wüthrich (2007).
Nuclear magnetic resonance structure of the N-terminal domain of nonstructural protein 3 from the severe acute respiratory syndrome coronavirus.
  J Virol, 81, 12049-12060.
PDB codes: 2gri 2idy
17295314 S.Tomić, B.Bertosa, T.Wang, and R.C.Wade (2007).
COMBINE analysis of the specificity of binding of Ras proteins to their effectors.
  Proteins, 67, 435-447.  
16531227 B.Ford, V.Hornak, H.Kleinman, and N.Nassar (2006).
Structure of a transient intermediate for GTP hydrolysis by ras.
  Structure, 14, 427-436.
PDB codes: 1zvq 1zw6
16428446 D.M.Truckses, J.E.Bloomekatz, and J.Thorner (2006).
The RA domain of Ste50 adaptor protein is required for delivery of Ste11 to the plasma membrane in the filamentous growth signaling pathway of the yeast Saccharomyces cerevisiae.
  Mol Cell Biol, 26, 912-928.  
16452984 H.Rehmann, J.Das, P.Knipscheer, A.Wittinghofer, and J.L.Bos (2006).
Structure of the cyclic-AMP-responsive exchange factor Epac2 in its auto-inhibited state.
  Nature, 439, 625-628.
PDB code: 2byv
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
16316996 Y.Li, S.Asuri, J.F.Rebhun, A.F.Castro, N.C.Paranavitana, and L.A.Quilliam (2006).
The RAP1 guanine nucleotide exchange factor Epac2 couples cyclic AMP and Ras signals at the plasma membrane.
  J Biol Chem, 281, 2506-2514.  
15878843 B.Ford, K.Skowronek, S.Boykevisch, D.Bar-Sagi, and N.Nassar (2005).
Structure of the G60A mutant of Ras: implications for the dominant negative effect.
  J Biol Chem, 280, 25697-25705.  
15994326 M.Ye, F.Shima, S.Muraoka, J.Liao, H.Okamoto, M.Yamamoto, A.Tamura, N.Yagi, T.Ueki, and T.Kataoka (2005).
Crystal structure of M-Ras reveals a GTP-bound "off" state conformation of Ras family small GTPases.
  J Biol Chem, 280, 31267-31275.
PDB codes: 1x1r 1x1s
15197281 C.Kiel, T.Selzer, Y.Shaul, G.Schreiber, and C.Herrmann (2004).
Electrostatically optimized Ras-binding Ral guanine dissociation stimulator mutants increase the rate of association by stabilizing the encounter complex.
  Proc Natl Acad Sci U S A, 101, 9223-9228.  
15653425 E.J.Helmreich (2004).
Structural flexibility of small GTPases. Can it explain their functional versatility?
  Biol Chem, 385, 1121-1136.  
14988733 I.Dreveny, H.Kondo, K.Uchiyama, A.Shaw, X.Zhang, and P.S.Freemont (2004).
Structural basis of the interaction between the AAA ATPase p97/VCP and its adaptor protein p47.
  EMBO J, 23, 1030-1039.
PDB code: 1s3s
15296756 S.Krugmann, R.Williams, L.Stephens, and P.T.Hawkins (2004).
ARAP3 is a PI3K- and rap-regulated GAP for RhoA.
  Curr Biol, 14, 1380-1384.  
12581669 C.Herrmann (2003).
Ras-effector interactions: after one decade.
  Curr Opin Struct Biol, 13, 122-129.  
12842038 G.Buhrman, V.de Serrano, and C.Mattos (2003).
Organic solvents order the dynamic switch II in Ras crystals.
  Structure, 11, 747-751.
PDB codes: 1p2s 1p2t 1p2u 1p2v
12910454 L.Oliveira, P.B.Paiva, A.C.Paiva, and G.Vriend (2003).
Identification of functionally conserved residues with the use of entropy-variability plots.
  Proteins, 52, 544-552.  
12692530 M.H.Kim, T.Cierpicki, U.Derewenda, D.Krowarsch, Y.Feng, Y.Devedjiev, Z.Dauter, C.A.Walsh, J.Otlewski, J.H.Bushweller, and Z.S.Derewenda (2003).
The DCX-domain tandems of doublecortin and doublecortin-like kinase.
  Nat Struct Biol, 10, 324-333.
PDB codes: 1mfw 1mg4 1mjd
12887891 M.I.Wilson, D.J.Gill, O.Perisic, M.T.Quinn, and R.L.Williams (2003).
PB1 domain-mediated heterodimerization in NADPH oxidase and signaling complexes of atypical protein kinase C with Par6 and p62.
  Mol Cell, 12, 39-50.
PDB code: 1oey
12839989 S.Fukai, H.T.Matern, J.R.Jagath, R.H.Scheller, and A.T.Brunger (2003).
Structural basis of the interaction between RalA and Sec5, a subunit of the sec6/8 complex.
  EMBO J, 22, 3267-3278.
PDB code: 1uad
12654246 T.Schwartz, and G.Blobel (2003).
Structural basis for the function of the beta subunit of the eukaryotic signal recognition particle receptor.
  Cell, 112, 793-803.
PDB code: 1nrj
11779480 J.E.Coyle, S.Qamar, K.R.Rajashankar, and D.B.Nikolov (2002).
Structure of GABARAP in two conformations: implications for GABA(A) receptor localization and tubulin binding.
  Neuron, 33, 63-74.  
11980706 M.Hanzal-Bayer, L.Renault, P.Roversi, A.Wittinghofer, and R.C.Hillig (2002).
The complex of Arl2-GTP and PDE delta: from structure to function.
  EMBO J, 21, 2095-2106.
PDB codes: 1ksg 1ksh 1ksj
11723130 M.Kido, F.Shima, T.Satoh, T.Asato, K.Kariya, and T.Kataoka (2002).
Critical function of the Ras-associating domain as a primary Ras-binding site for regulation of Saccharomyces cerevisiae adenylyl cyclase.
  J Biol Chem, 277, 3117-3123.  
12151228 S.Djordjevic, and P.C.Driscoll (2002).
Structural insight into substrate specificity and regulatory mechanisms of phosphoinositide 3-kinases.
  Trends Biochem Sci, 27, 426-432.  
11812780 T.Brinkmann, O.Daumke, U.Herbrand, D.Kühlmann, P.Stege, M.R.Ahmadian, and A.Wittinghofer (2002).
Rap-specific GTPase activating protein follows an alternative mechanism.
  J Biol Chem, 277, 12525-12531.  
11748241 T.Linnemann, C.Kiel, P.Herter, and C.Herrmann (2002).
The activation of RalGDS can be achieved independently of its Ras binding domain. Implications of an activation mechanism in Ras effector specificity and signal distribution.
  J Biol Chem, 277, 7831-7837.  
11483498 H.Terasawa, Y.Noda, T.Ito, H.Hatanaka, S.Ichikawa, K.Ogura, H.Sumimoto, and F.Inagaki (2001).
Structure and ligand recognition of the PB1 domain: a novel protein module binding to the PC motif.
  EMBO J, 20, 3947-3956.
PDB codes: 1ip9 1ipg
11166556 I.Callebaut, J.de Gunzburg, B.Goud, and J.P.Mornon (2001).
RUN domains: a new family of domains involved in Ras-like GTPase signaling.
  Trends Biochem Sci, 26, 79-83.  
11701921 I.R.Vetter, and A.Wittinghofer (2001).
The guanine nucleotide-binding switch in three dimensions.
  Science, 294, 1299-1304.  
11738594 K.D.Corbett, and T.Alber (2001).
The many faces of Ras: recognition of small GTP-binding proteins.
  Trends Biochem Sci, 26, 710-716.  
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
11320243 M.Spoerner, C.Herrmann, I.R.Vetter, H.R.Kalbitzer, and A.Wittinghofer (2001).
Dynamic properties of the Ras switch I region and its importance for binding to effectors.
  Proc Natl Acad Sci U S A, 98, 4944-4949.
PDB code: 1iaq
10684602 D.Owen, H.R.Mott, E.D.Laue, and P.N.Lowe (2000).
Residues in Cdc42 that specify binding to individual CRIB effector proteins.
  Biochemistry, 39, 1243-1250.  
10970839 K.Hamada, T.Shimizu, T.Matsui, S.Tsukita, and T.Hakoshima (2000).
Structural basis of the membrane-targeting and unmasking mechanisms of the radixin FERM domain.
  EMBO J, 19, 4449-4462.
PDB codes: 1gc6 1gc7
  11090627 K.Lapouge, S.J.Smith, P.A.Walker, S.J.Gamblin, S.J.Smerdon, and K.Rittinger (2000).
Structure of the TPR domain of p67phox in complex with Rac.GTP.
  Mol Cell, 6, 899-907.
PDB code: 1e96
10205047 C.E.Stebbins, W.G.Kaelin, and N.P.Pavletich (1999).
Structure of the VHL-ElonginC-ElonginB complex: implications for VHL tumor suppressor function.
  Science, 284, 455-461.
PDB code: 1vcb
10025402 C.Ostermeier, and A.T.Brunger (1999).
Structural basis of Rab effector specificity: crystal structure of the small G protein Rab3A complexed with the effector domain of rabphilin-3A.
  Cell, 96, 363-374.
PDB code: 1zbd
10367892 I.R.Vetter, A.Arndt, U.Kutay, D.Görlich, and A.Wittinghofer (1999).
Structural view of the Ran-Importin beta interaction at 2.3 A resolution.
  Cell, 97, 635-646.
PDB code: 1ibr
10196191 N.van den Berghe, R.H.Cool, and A.Wittinghofer (1999).
Discriminatory residues in Ras and Rap for guanine nucleotide exchange factor recognition.
  J Biol Chem, 274, 11078-11085.  
10514434 R.Li, B.Debreceni, B.Jia, Y.Gao, G.Tigyi, and Y.Zheng (1999).
Localization of the PAK1-, WASP-, and IQGAP1-specifying regions of Cdc42.
  J Biol Chem, 274, 29648-29654.  
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.  
10619026 R.Maesaki, K.Ihara, T.Shimizu, S.Kuroda, K.Kaibuchi, and T.Hakoshima (1999).
The structural basis of Rho effector recognition revealed by the crystal structure of human RhoA complexed with the effector domain of PKN/PRK1.
  Mol Cell, 4, 793-803.
PDB code: 1cxz
10583404 S.Müller, C.von Eichel-Streiber, and M.Moos (1999).
Impact of amino acids 22-27 of Rho-subfamily GTPases on glucosylation by the large clostridial cytotoxins TcsL-1522, TcdB-1470 and TcdB-8864.
  Eur J Biochem, 266, 1073-1080.  
10224125 T.Linnemann, M.Geyer, B.K.Jaitner, C.Block, H.R.Kalbitzer, A.Wittinghofer, and C.Herrmann (1999).
Thermodynamic and kinetic characterization of the interaction between the Ras binding domain of AF6 and members of the Ras subfamily.
  J Biol Chem, 274, 13556-13562.  
10608844 Y.Liao, K.Kariya, C.D.Hu, M.Shibatohge, M.Goshima, T.Okada, Y.Watari, X.Gao, T.G.Jin, Y.Yamawaki-Kataoka, and T.Kataoka (1999).
RA-GEF, a novel Rap1A guanine nucleotide exchange factor containing a Ras/Rap1A-associating domain, is conserved between nematode and humans.
  J Biol Chem, 274, 37815-37820.  
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.