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PDBsum entry 1foe
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protein ligands Protein-protein interface(s) links
Signaling protein, immune system/signali PDB id
1foe

 

 

 

 

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Contents
Protein chains
368 a.a. *
177 a.a. *
Ligands
SO4 ×4
Waters ×93
* Residue conservation analysis
PDB id:
1foe
Name: Signaling protein, immune system/signali
Title: Crystal structure of rac1 in complex with the guanine nucleotide exchange region of tiam1
Structure: T-lymphoma invasion and metastasis inducing protein 1. Chain: a, c, e, g. Fragment: residues 1033 to 1406 from murine t-lymphoma invasion and metastasis factor 1, pleckstrin homology domain. Synonym: tiam1 protein, t-cell lymphoma invasion and metastasis 1. Engineered: yes. Mutation: yes. Other_details: ala-met-gly cloning artifact added to n-terminus. Ras-related c3 botulinum toxin substrate.
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606.
Biol. unit: Dimer (from PQS)
Resolution:
2.80Å     R-factor:   0.262     R-free:   0.293
Authors: D.K.Worthylake,K.L.Rossman,J.Sondek
Key ref:
D.K.Worthylake et al. (2000). Crystal structure of Rac1 in complex with the guanine nucleotide exchange region of Tiam1. Nature, 408, 682-688. PubMed id: 11130063 DOI: 10.1038/35047014
Date:
27-Aug-00     Release date:   17-Jan-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q60610  (TIAM1_MOUSE) -  Rho guanine nucleotide exchange factor TIAM1 from Mus musculus
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1591 a.a.
368 a.a.
Protein chains
Pfam   ArchSchema ?
P63000  (RAC1_HUMAN) -  Ras-related C3 botulinum toxin substrate 1 from Homo sapiens
Seq:
Struc: 		192 a.a.
177 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains B, D, F, H: E.C.3.6.5.2  - small monomeric GTPase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: GTP + H2O = GDP + phosphate + H+
GTP
 + H2O
 = GDP
 + phosphate
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1038/35047014 Nature 408:682-688 (2000)
PubMed id: 11130063  
 
 
Crystal structure of Rac1 in complex with the guanine nucleotide exchange region of Tiam1.
D.K.Worthylake, K.L.Rossman, J.Sondek.
 
  ABSTRACT  
 
The principal guanine nucleotide exchange factors for Rho family G proteins contain tandem Dbl-homology (DH) and pleckstrin-homology (PH) domains that catalyse nucleotide exchange and the activation of G proteins. Here we have determined the crystal structure of the DH and PH domains of the T-lymphoma invasion and metastasis factor 1 (Tiam1) protein in complex with its cognate Rho family G protein, Rac1. The two switch regions of Rac1 are stabilized in conformations that disrupt both magnesium binding and guanine nucleotide interaction. The resulting cleft in Rac1 is devoid of nucleotide and highly exposed to solvent. The PH domain of Tiam1 does not contact Rac1, and the position and orientation of the PH domain is markedly altered relative to the structure of the uncomplexed, GTPase-free DH/PH element from Sos1. The Tiam1/Rac1 structure highlights the interactions that catalyse nucleotide exchange on Rho family G proteins, and illustrates structural determinants dictating specificity between individual Rho family members and their associated Dbl-related guanine nucleotide exchange factors.
 
  Selected figure(s)  
 
Figure 2.
Figure 2: Structural comparison of the Tiam1/Rac1 complex with the Sos1 DH/PH domains. a, The Tiam1/Rac1 complex. Switch regions of Rac1 are red; the rest of the G protein is green. Tiam1 DH and PH domains are yellow and blue, respectively; disordered regions are orange; and black dashed line highlights 9 and its equivalent in Sos1 (c). b, View in a rotated 90° about the horizontal. c, Structure of the Sos1 DH (yellow) and PH (blue) domains15 aligned with Tiam1 orientated as in a by least squares superposition of the 72 -carbon atoms of CR1-CR3 (r.m.s. deviations, 1.52 Å). Yellow dashed line indicates disordered residues in the Sos1 DH domain. d, View in c rotated 90° about the horizontal. Note, position of the Sos1 PH domain overlaps the G-protein-binding interface. Figures 2, 5 and 6c were made using MOLSCRIPT40 and Raster3D^41. 		Figure 3.
Figure 3: Representation of Tiam1/Rac1 interface contacts. The model of Rac1 on the left in green (with switch regions in red) has been rotated 180° about the vertical axis from its relative orientation with respect to the DH domain (on right in yellow) to display the two interface surfaces. Residues in black type lose >10 Å2 of accessible surface area on complex formation. Associated intermolecular contacts are listed below, colour coded by interaction type (red, van der Waal's; green, hydrogen bonds; blue, ionic) and starred if non-ionic but involving side-chain atoms. Figure was made using Ribbons42.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2000, 408, 682-688) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21779026 R.Garcia-Mata, E.Boulter, and K.Burridge (2011).
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20585582 K.F.Ahmad, and W.A.Lim (2010).
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  PLoS One, 5, e11291.
PDB code: 3jv3
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Structure and function of heterotrimeric G protein-regulated Rho guanine nucleotide exchange factors.
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The PHCCEx domain of Tiam1/2 is a novel protein- and membrane-binding module.
  EMBO J, 29, 236-250.
PDB codes: 3a8n 3a8p 3a8q
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19745154 J.Yang, Z.Zhang, S.M.Roe, C.J.Marshall, and D.Barford (2009).
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PDB codes: 2wm9 2wmn 2wmo
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19549603 N.Bouquier, E.Vignal, S.Charrasse, M.Weill, S.Schmidt, J.P.Léonetti, A.Blangy, and P.Fort (2009).
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19153575 W.Feng, and M.Zhang (2009).
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PDB code: 3gcg
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Remedial strategies in structural proteomics: expression, purification, and crystallization of the Vav1/Rac1 complex.
  Protein Expr Purif, 53, 51-62.  
17506639 A.Cook, F.Bono, M.Jinek, and E.Conti (2007).
Structural biology of nucleocytoplasmic transport.
  Annu Rev Biochem, 76, 647-671.  
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Specificity and mechanism of action of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases.
  J Biol Chem, 282, 35666-35678.  
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.
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  Mol Cell, 25, 455-462.
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17540168 J.L.Bos, H.Rehmann, and A.Wittinghofer (2007).
GEFs and GAPs: critical elements in the control of small G proteins.
  Cell, 129, 865-877.  
17264933 J.M.Davis, L.K.Tsou, and A.D.Hamilton (2007).
Synthetic non-peptide mimetics of alpha-helices.
  Chem Soc Rev, 36, 326-334.  
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Crystal structure of the rac activator, Asef, reveals its autoinhibitory mechanism.
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Auto-inhibition of the Dbl family protein Tim by an N-terminal helical motif.
  J Biol Chem, 282, 13813-13823.  
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  Nat Struct Mol Biol, 14, 814-823.
PDB code: 2pz1
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Asymmetric coiled-coil structure with Guanine nucleotide exchange activity.
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  Proc Natl Acad Sci U S A, 104, 8305-8310.
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PDB code: 2fu5
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Cell migration and signaling specificity is determined by the phosphatidylserine recognition motif of Rac1.
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Interactions of UNC-34 Enabled with Rac GTPases and the NIK kinase MIG-15 in Caenorhabditis elegans axon pathfinding and neuronal migration.
  Genetics, 172, 893-913.  
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Crystal structure of Rac1 bound to its effector phospholipase C-beta2.
  Nat Struct Mol Biol, 13, 1135-1140.
PDB code: 2fju
17072882 P.García, V.Tajadura, I.García, and Y.Sánchez (2006).
Role of Rho GTPases and Rho-GEFs in the regulation of cell shape and integrity in fission yeast.
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Analysis of protein hydration in ultrahigh-resolution structures of the SRP GTPase Ffh.
  Acta Crystallogr D Biol Crystallogr, 62, 1520-1534.
PDB codes: 2j45 2j46
16613852 Z.Liu, E.V.Kostenko, G.M.Mahon, O.O.Olabisi, and I.P.Whitehead (2006).
Transformation by the Rho-specific guanine nucleotide exchange factor Dbs requires ROCK I-mediated phosphorylation of myosin light chain.
  J Biol Chem, 281, 16043-16051.  
15980860 A.Berken, C.Thomas, and A.Wittinghofer (2005).
A new family of RhoGEFs activates the Rop molecular switch in plants.
  Nature, 436, 1176-1180.  
15557278 A.Mizrahi, S.Molshanski-Mor, C.Weinbaum, Y.Zheng, M.Hirshberg, and E.Pick (2005).
Activation of the phagocyte NADPH oxidase by Rac Guanine nucleotide exchange factors in conjunction with ATP and nucleoside diphosphate kinase.
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16004878 C.A.Johnston, F.S.Willard, M.R.Jezyk, Z.Fredericks, E.T.Bodor, M.B.Jones, R.Blaesius, V.J.Watts, T.K.Harden, J.Sondek, J.K.Ramer, and D.P.Siderovski (2005).
Structure of Galpha(i1) bound to a GDP-selective peptide provides insight into guanine nucleotide exchange.
  Structure, 13, 1069-1080.
PDB code: 1y3a
15747061 C.R.McCudden, M.D.Hains, R.J.Kimple, D.P.Siderovski, and F.S.Willard (2005).
G-protein signaling: back to the future.
  Cell Mol Life Sci, 62, 551-577.  
15611121 H.Qin, H.S.Carr, X.Wu, D.Muallem, N.H.Tran, and J.A.Frost (2005).
Characterization of the biochemical and transforming properties of the neuroepithelial transforming protein 1.
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15545267 K.Hill, S.Krugmann, S.R.Andrews, W.J.Coadwell, P.Finan, H.C.Welch, P.T.Hawkins, and L.R.Stephens (2005).
Regulation of P-Rex1 by phosphatidylinositol (3,4,5)-trisphosphate and Gbetagamma subunits.
  J Biol Chem, 280, 4166-4173.  
15688002 K.L.Rossman, C.J.Der, and J.Sondek (2005).
GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors.
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15817389 K.L.Rossman, and J.Sondek (2005).
Larger than Dbl: new structural insights into RhoA activation.
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15939335 M.Arkin (2005).
Protein-protein interactions and cancer: small molecules going in for the kill.
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15775967 O.Llorca, E.Arias-Palomo, J.L.Zugaza, and X.R.Bustelo (2005).
Global conformational rearrangements during the activation of the GDP/GTP exchange factor Vav3.
  EMBO J, 24, 1330-1340.  
15897194 R.E.Joseph, and F.A.Norris (2005).
Substrate specificity and recognition is conferred by the pleckstrin homology domain of the Dbl family guanine nucleotide exchange factor P-Rex2.
  J Biol Chem, 280, 27508-27512.  
16103122 R.Pereira, and R.A.Cerione (2005).
A switch 3 point mutation in the alpha subunit of transducin yields a unique dominant-negative inhibitor.
  J Biol Chem, 280, 35696-35703.  
15635100 S.E.Martínez, L.Yuan, C.Lacza, H.Ransom, G.M.Mahon, I.P.Whitehead, and L.E.Hake (2005).
XGef mediates early CPEB phosphorylation during Xenopus oocyte meiotic maturation.
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Structure, exchange determinants, and family-wide rab specificity of the tandem helical bundle and Vps9 domains of Rabex-5.
  Cell, 118, 607-617.
PDB code: 1txu
14999155 A.E.Karnoub, M.Symons, S.L.Campbell, and C.J.Der (2004).
Molecular basis for Rho GTPase signaling specificity.
  Breast Cancer Res Treat, 84, 61-71.  
15039571 A.Oleksy, H.Barton, Y.Devedjiev, M.Purdy, U.Derewenda, J.Otlewski, and Z.S.Derewenda (2004).
Preliminary crystallographic analysis of the complex of the human GTPase RhoA with the DH/PH tandem of PDZ-RhoGEF.
  Acta Crystallogr D Biol Crystallogr, 60, 740-742.  
15322108 B.Bryan, V.Kumar, L.J.Stafford, Y.Cai, G.Wu, and M.Liu (2004).
GEFT, a Rho family guanine nucleotide exchange factor, regulates neurite outgrowth and dendritic spine formation.
  J Biol Chem, 279, 45824-45832.  
14597635 B.Debreceni, Y.Gao, F.Guo, K.Zhu, B.Jia, and Y.Zheng (2004).
Mechanisms of guanine nucleotide exchange and Rac-mediated signaling revealed by a dominant negative trio mutant.
  J Biol Chem, 279, 3777-3786.  
14638695 C.M.Grimsley, J.M.Kinchen, A.C.Tosello-Trampont, E.Brugnera, L.B.Haney, M.Lu, Q.Chen, D.Klingele, M.O.Hengartner, and K.S.Ravichandran (2004).
Dock180 and ELMO1 proteins cooperate to promote evolutionarily conserved Rac-dependent cell migration.
  J Biol Chem, 279, 6087-6097.  
15292195 C.Weiss-Haljiti, C.Pasquali, H.Ji, C.Gillieron, C.Chabert, M.L.Curchod, E.Hirsch, A.J.Ridley, R.H.van Huijsduijnen, M.Camps, and C.Rommel (2004).
Involvement of phosphoinositide 3-kinase gamma, Rac, and PAK signaling in chemokine-induced macrophage migration.
  J Biol Chem, 279, 43273-43284.  
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Alternative splicing of Rac1 generates Rac1b, a self-activating GTPase.
  J Biol Chem, 279, 4743-4749.
PDB codes: 1ryf 1ryh
15274927 D.K.Worthylake, K.L.Rossman, and J.Sondek (2004).
Crystal structure of the DH/PH fragment of Dbs without bound GTPase.
  Structure, 12, 1078-1086.
PDB code: 1rj2
15457207 D.Komander, A.Fairservice, M.Deak, G.S.Kular, A.R.Prescott, C.Peter Downes, S.T.Safrany, D.R.Alessi, and D.M.van Aalten (2004).
Structural insights into the regulation of PDK1 by phosphoinositides and inositol phosphates.
  EMBO J, 23, 3918-3928.
PDB codes: 1w1d 1w1g 1w1h
15507210 H.Sondermann, S.M.Soisson, S.Boykevisch, S.S.Yang, D.Bar-Sagi, and J.Kuriyan (2004).
Structural analysis of autoinhibition in the Ras activator Son of sevenless.
  Cell, 119, 393-405.
PDB codes: 1xd2 1xd4 1xdv
15199069 K.R.Skowronek, F.Guo, Y.Zheng, and N.Nassar (2004).
The C-terminal basic tail of RhoG assists the guanine nucleotide exchange factor trio in binding to phospholipids.
  J Biol Chem, 279, 37895-37907.
PDB code: 1nty
14701795 L.Cheng, G.M.Mahon, E.V.Kostenko, and I.P.Whitehead (2004).
Pleckstrin homology domain-mediated activation of the rho-specific guanine nucleotide exchange factor Dbs by Rac1.
  J Biol Chem, 279, 12786-12793.  
15247908 M.Lu, J.M.Kinchen, K.L.Rossman, C.Grimsley, C.deBakker, E.Brugnera, A.C.Tosello-Trampont, L.B.Haney, D.Klingele, J.Sondek, M.O.Hengartner, and K.S.Ravichandran (2004).
PH domain of ELMO functions in trans to regulate Rac activation via Dock180.
  Nat Struct Mol Biol, 11, 756-762.  
15016378 M.Miaczynska, S.Christoforidis, A.Giner, A.Shevchenko, S.Uttenweiler-Joseph, B.Habermann, M.Wilm, R.G.Parton, and M.Zerial (2004).
APPL proteins link Rab5 to nuclear signal transduction via an endosomal compartment.
  Cell, 116, 445-456.  
15247287 N.Meller, M.Irani-Tehrani, B.I.Ratnikov, B.M.Paschal, and M.A.Schwartz (2004).
The novel Cdc42 guanine nucleotide exchange factor, zizimin1, dimerizes via the Cdc42-binding CZH2 domain.
  J Biol Chem, 279, 37470-37476.  
15306850 Q.Feng, D.Baird, and R.A.Cerione (2004).
Novel regulatory mechanisms for the Dbl family guanine nucleotide exchange factor Cool-2/alpha-Pix.
  EMBO J, 23, 3492-3504.  
15577926 R.Dvorsky, and M.R.Ahmadian (2004).
Always look on the bright site of Rho: structural implications for a conserved intermolecular interface.
  EMBO Rep, 5, 1130-1136.  
15331592 R.Kristelly, G.Gao, and J.J.Tesmer (2004).
Structural determinants of RhoA binding and nucleotide exchange in leukemia-associated Rho guanine-nucleotide exchange factor.
  J Biol Chem, 279, 47352-47362.
PDB codes: 1txd 1x86
15302837 S.Barale, D.McCusker, and R.A.Arkowitz (2004).
The exchange factor Cdc24 is required for cell fusion during yeast mating.
  Eukaryot Cell, 3, 1049-1061.  
14681227 T.Boesen, S.S.Mohammad, G.D.Pavitt, and G.R.Andersen (2004).
Structure of the catalytic fragment of translation initiation factor 2B and identification of a critically important catalytic residue.
  J Biol Chem, 279, 10584-10592.
PDB code: 1paq
15128949 Y.Gao, J.B.Dickerson, F.Guo, J.Zheng, and Y.Zheng (2004).
Rational design and characterization of a Rac GTPase-specific small molecule inhibitor.
  Proc Natl Acad Sci U S A, 101, 7618-7623.  
12637530 E.J.Fuentes, A.E.Karnoub, M.A.Booden, C.J.Der, and S.L.Campbell (2003).
Critical role of the pleckstrin homology domain in Dbs signaling and growth regulation.
  J Biol Chem, 278, 21188-21196.  
14690595 E.Mossessova, R.A.Corpina, and J.Goldberg (2003).
Crystal structure of ARF1*Sec7 complexed with Brefeldin A and its implications for the guanine nucleotide exchange mechanism.
  Mol Cell, 12, 1403-1411.
PDB code: 1re0
12682071 F.Spitzenberger, S.Pietropaolo, P.Verkade, B.Habermann, S.Lacas-Gervais, H.Mziaut, M.Pietropaolo, and M.Solimena (2003).
Islet cell autoantigen of 69 kDa is an arfaptin-related protein associated with the Golgi complex of insulinoma INS-1 cells.
  J Biol Chem, 278, 26166-26173.  
12885767 G.E.Cozier, D.Bouyoucef, and P.J.Cullen (2003).
Engineering the phosphoinositide-binding profile of a class I pleckstrin homology domain.
  J Biol Chem, 278, 39489-39496.  
12433916 G.Zhu, J.Liu, S.Terzyan, P.Zhai, G.Li, and X.C.Zhang (2003).
High resolution crystal structures of human Rab5a and five mutants with substitutions in the catalytically important phosphate-binding loop.
  J Biol Chem, 278, 2452-2460.
PDB codes: 1n6h 1n6i 1n6k 1n6l 1n6n 1n6o 1n6p 1n6r
14656442 H.Sondermann, S.M.Soisson, D.Bar-Sagi, and J.Kuriyan (2003).
Tandem histone folds in the structure of the N-terminal segment of the ras activator Son of Sevenless.
  Structure, 11, 1583-1593.
PDB code: 1q9c
12517447 J.Cherfils, and M.Chabre (2003).
Activation of G-protein Galpha subunits by receptors through Galpha-Gbeta and Galpha-Ggamma interactions.
  Trends Biochem Sci, 28, 13-17.  
12637522 K.L.Rossman, L.Cheng, G.M.Mahon, R.J.Rojas, J.T.Snyder, I.P.Whitehead, and J.Sondek (2003).
Multifunctional roles for the PH domain of Dbs in regulating Rho GTPase activation.
  J Biol Chem, 278, 18393-18400.  
12471028 K.Robbe, A.Otto-Bruc, P.Chardin, and B.Antonny (2003).
Dissociation of GDP dissociation inhibitor and membrane translocation are required for efficient activation of Rac by the Dbl homology-pleckstrin homology region of Tiam.
  J Biol Chem, 278, 4756-4762.  
12832783 K.Skowronek, M.Ghumman, Y.Zheng, and N.Nassar (2003).
Crystallization and initial crystal characterization of the N-terminal DH/PH domain of Trio.
  Acta Crystallogr D Biol Crystallogr, 59, 1273-1275.  
14654833 L.Renault, B.Guibert, and J.Cherfils (2003).
Structural snapshots of the mechanism and inhibition of a guanine nucleotide exchange factor.
  Nature, 426, 525-530.
PDB codes: 1r8m 1r8q 1r8r 1r8s 1s9d
12888567 L.S.Price, M.Langeslag, J.P.ten Klooster, P.L.Hordijk, K.Jalink, and J.G.Collard (2003).
Calcium signaling regulates translocation and activation of Rac.
  J Biol Chem, 278, 39413-39421.  
12525493 M.A.Baumeister, L.Martinu, K.L.Rossman, J.Sondek, M.A.Lemmon, and M.M.Chou (2003).
Loss of phosphatidylinositol 3-phosphate binding by the C-terminal Tiam-1 pleckstrin homology domain prevents in vivo Rac1 activation without affecting membrane targeting.
  J Biol Chem, 278, 11457-11464.  
12719429 M.C.Schlumberger, A.Friebel, G.Buchwald, K.Scheffzek, A.Wittinghofer, and W.D.Hardt (2003).
Amino acids of the bacterial toxin SopE involved in G nucleotide exchange on Cdc42.
  J Biol Chem, 278, 27149-27159.  
12475976 N.Sigal, Y.Gorzalczany, R.Sarfstein, C.Weinbaum, Y.Zheng, and E.Pick (2003).
The guanine nucleotide exchange factor trio activates the phagocyte NADPH oxidase in the absence of GDP to GTP exchange on Rac. "The emperor's nw clothes".
  J Biol Chem, 278, 4854-4861.  
14501138 R.Kristelly, B.T.Earnest, L.Krishnamoorthy, and J.J.Tesmer (2003).
Preliminary structure analysis of the DH/PH domains of leukemia-associated RhoGEF.
  Acta Crystallogr D Biol Crystallogr, 59, 1859-1862.  
12972602 T.J.Kubiseski, J.Culotti, and T.Pawson (2003).
Functional analysis of the Caenorhabditis elegans UNC-73B PH domain demonstrates a role in activation of the Rac GTPase in vitro and axon guidance in vivo.
  Mol Cell Biol, 23, 6823-6835.  
12547822 X.Guo, L.J.Stafford, B.Bryan, C.Xia, W.Ma, X.Wu, D.Liu, Z.Songyang, and M.Liu (2003).
A Rac/Cdc42-specific exchange factor, GEFT, induces cell proliferation, transformation, and migration.
  J Biol Chem, 278, 13207-13215.  
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
11955434 H.C.Welch, W.J.Coadwell, C.D.Ellson, G.J.Ferguson, S.R.Andrews, H.Erdjument-Bromage, P.Tempst, P.T.Hawkins, and L.R.Stephens (2002).
P-Rex1, a PtdIns(3,4,5)P3- and Gbetagamma-regulated guanine-nucleotide exchange factor for Rac.
  Cell, 108, 809-821.  
11744709 H.J.Wieden, K.Gromadski, D.Rodnin, and M.V.Rodnina (2002).
Mechanism of elongation factor (EF)-Ts-catalyzed nucleotide exchange in EF-Tu. Contribution of contacts at the guanine base.
  J Biol Chem, 277, 6032-6036.  
11919635 J.Ng, T.Nardine, M.Harms, J.Tzu, A.Goldstein, Y.Sun, G.Dietzl, B.J.Dickson, and L.Luo (2002).
Rac GTPases control axon growth, guidance and branching.
  Nature, 416, 442-447.  
12006984 J.T.Snyder, D.K.Worthylake, K.L.Rossman, L.Betts, W.M.Pruitt, D.P.Siderovski, C.J.Der, and J.Sondek (2002).
Structural basis for the selective activation of Rho GTPases by Dbl exchange factors.
  Nat Struct Biol, 9, 468-475.
PDB codes: 1ki1 1lb1
11889037 K.L.Rossman, D.K.Worthylake, J.T.Snyder, D.P.Siderovski, S.L.Campbell, and J.Sondek (2002).
A crystallographic view of interactions between Dbs and Cdc42: PH domain-assisted guanine nucleotide exchange.
  EMBO J, 21, 1315-1326.
PDB codes: 1kz7 1kzg
12401782 K.L.Rossman, D.K.Worthylake, J.T.Snyder, L.Cheng, I.P.Whitehead, and J.Sondek (2002).
Functional analysis of cdc42 residues required for Guanine nucleotide exchange.
  J Biol Chem, 277, 50893-50898.  
12215546 L.Cheng, K.L.Rossman, G.M.Mahon, D.K.Worthylake, M.Korus, J.Sondek, and I.P.Whitehead (2002).
RhoGEF specificity mutants implicate RhoA as a target for Dbs transforming activity.
  Mol Cell Biol, 22, 6895-6905.  
11900529 R.Thapar, A.E.Karnoub, and S.L.Campbell (2002).
Structural and biophysical insights into the role of the insert region in Rac1 function.
  Biochemistry, 41, 3875-3883.  
12177050 T.R.Palmby, K.Abe, and C.J.Der (2002).
Critical role of the pleckstrin homology and cysteine-rich domains in Vav signaling and transforming activity.
  J Biol Chem, 277, 39350-39359.  
11685227 A.E.Karnoub, D.K.Worthylake, K.L.Rossman, W.M.Pruitt, S.L.Campbell, J.Sondek, and C.J.Der (2001).
Molecular basis for Rac1 recognition by guanine nucleotide exchange factors.
  Nat Struct Biol, 8, 1037-1041.  
11701921 I.R.Vetter, and A.Wittinghofer (2001).
The guanine nucleotide-binding switch in three dimensions.
  Science, 294, 1299-1304.  
11577097 J.T.Snyder, K.L.Rossman, M.A.Baumeister, W.M.Pruitt, D.P.Siderovski, C.J.Der, M.A.Lemmon, and J.Sondek (2001).
Quantitative analysis of the effect of phosphoinositide interactions on the function of Dbl family proteins.
  J Biol Chem, 276, 45868-45875.  
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.  
11470431 K.L.Longenecker, M.E.Lewis, H.Chikumi, J.S.Gutkind, and Z.S.Derewenda (2001).
Structure of the RGS-like domain from PDZ-RhoGEF: linking heterotrimeric g protein-coupled signaling to Rho GTPases.
  Structure, 9, 559-569.
PDB code: 1htj
11336674 L.Renault, J.Kuhlmann, A.Henkel, and A.Wittinghofer (2001).
Structural basis for guanine nucleotide exchange on Ran by the regulator of chromosome condensation (RCC1).
  Cell, 105, 245-255.
PDB code: 1i2m
11344266 P.Rondard, T.Iiri, S.Srinivasan, E.Meng, T.Fujita, and H.R.Bourne (2001).
Mutant G protein alpha subunit activated by Gbeta gamma: a model for receptor activation?
  Proc Natl Acad Sci U S A, 98, 6150-6155.  
11448995 P.Young, E.Ehler, and M.Gautel (2001).
Obscurin, a giant sarcomeric Rho guanine nucleotide exchange factor protein involved in sarcomere assembly.
  J Cell Biol, 154, 123-136.  
11295560 S.Sprang (2001).
GEFs: master regulators of G-protein activation.
  Trends Biochem Sci, 26, 266-267.  
11595749 Y.Gao, J.Xing, M.Streuli, T.L.Leto, and Y.Zheng (2001).
Trp(56) of rac1 specifies interaction with a subset of guanine nucleotide exchange factors.
  J Biol Chem, 276, 47530-47541.  
11738596 Y.Zheng (2001).
Dbl family guanine nucleotide exchange factors.
  Trends Biochem Sci, 26, 724-732.  
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 code is shown on the right.

 

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