PDBsum entry 1hh4

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protein ligands metals Protein-protein interface(s) links
Signaling protein/inhibitor PDB id
Protein chains
189 a.a. *
186 a.a. *
GDP ×2
GER ×2
_MG ×2
Waters ×30
* Residue conservation analysis
PDB id:
Name: Signaling protein/inhibitor
Title: Rac1-rhogdi complex involved in NADPH oxidase activation
Structure: Ras-related c3 botulinum toxin substrate 1. Chain: a, b. Synonym: p21-rac1, ras-like protein tc25. Engineered: yes. Rho gdp-dissociation inhibitor 1. Chain: d, e. Synonym: rho gdi 1, rho-gdi alpha. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.
Biol. unit: Hetero-Dimer (from PDB file)
2.7Å     R-factor:   0.256     R-free:   0.280
Authors: S.Grizot,J.Faure,F.Fieschi,P.V.Vignais,M.-C.Dagher, E.Pebay-Peyroula
Key ref:
S.Grizot et al. (2001). Crystal structure of the Rac1-RhoGDI complex involved in nadph oxidase activation. Biochemistry, 40, 10007-10013. PubMed id: 11513578 DOI: 10.1021/bi010288k
20-Dec-00     Release date:   28-Aug-01    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P63000  (RAC1_HUMAN) -  Ras-related C3 botulinum toxin substrate 1
192 a.a.
189 a.a.*
Protein chains
Pfam   ArchSchema ?
P52565  (GDIR1_HUMAN) -  Rho GDP-dissociation inhibitor 1
204 a.a.
186 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   21 terms 
  Biological process     epithelial cell morphogenesis   86 terms 
  Biochemical function     nucleotide binding     12 terms  


DOI no: 10.1021/bi010288k Biochemistry 40:10007-10013 (2001)
PubMed id: 11513578  
Crystal structure of the Rac1-RhoGDI complex involved in nadph oxidase activation.
S.Grizot, J.Fauré, F.Fieschi, P.V.Vignais, M.C.Dagher, E.Pebay-Peyroula.
A heterodimer of prenylated Rac1 and Rho GDP dissociation inhibitor was purified and found to be competent in NADPH oxidase activation. Small angle neutron scattering experiments confirmed a 1:1 stoichiometry. The crystal structure of the Rac1-RhoGDI complex was determined at 2.7 A resolution. In this complex in which Rac1 is bound to GDP, the switch I region of Rac1 is in the GDP conformation whereas the switch II region resembles that of a GTP-bound GTPase. Two types of interaction between RhoGTPases and RhoGDI were investigated. The lipid-protein interaction between the geranylgeranyl moiety of Rac1 and RhoGDI resulted in numerous structural changes in the core of RhoGDI. The interactions between Rac1 and RhoGDI occur through hydrogen bonds which involve a number of residues of Rac1, namely, Tyr64(Rac), Arg66(Rac), His103(Rac), and His104(Rac), conserved within the Rho family and localized in the switch II region or in its close neighborhood. Moreover, in the switch II region of Rac1, hydrophobic interactions involving Leu67(Rac) and Leu70(Rac) contribute to the stability of the Rac1-RhoGDI complex. Inhibition of the GDP-GTP exchange in Rac1 upon binding to RhoGDI partly results from interaction of Thr35(Rac) with Asp45(GDI). In the Rac1-RhoGDI complex, the accessibility of the effector loops of Rac1 probably accounts for the ability of the Rac1-RhoGDI complex to activate the NADPH oxidase.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21779026 R.Garcia-Mata, E.Boulter, and K.Burridge (2011).
The 'invisible hand': regulation of RHO GTPases by RHOGDIs.
  Nat Rev Mol Cell Biol, 12, 493-504.  
  21492154 V.Zazueta-Novoa, G.Martínez-Cadena, G.M.Wessel, R.Zazueta-Sandoval, L.Castellano, and J.García-Soto (2011).
Concordance and interaction of guanine nucleotide dissociation inhibitor (RhoGDI) with RhoA in oogenesis and early development of the sea urchin.
  Dev Growth Differ, 53, 427-439.  
20472934 A.Dovas, Y.Choi, A.Yoneda, H.A.Multhaupt, S.H.Kwon, D.Kang, E.S.Oh, and J.R.Couchman (2010).
Serine 34 phosphorylation of rho guanine dissociation inhibitor (RhoGDIalpha) links signaling from conventional protein kinase C to RhoGTPase in cell adhesion.
  J Biol Chem, 285, 23296-23308.  
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.  
19765647 H.Bielek, A.Anselmo, and C.Dermardirossian (2009).
Morphological and proliferative abnormalities in renal mesangial cells lacking RhoGDI.
  Cell Signal, 21, 1974-1983.  
19534724 K.Miyano, H.Koga, R.Minakami, and H.Sumimoto (2009).
The insert region of the Rac GTPases is dispensable for activation of superoxide-producing NADPH oxidases.
  Biochem J, 422, 373-382.  
18846587 M.Alexander, M.Gerauer, M.Pechlivanis, B.Popkirova, R.Dvorsky, L.Brunsveld, H.Waldmann, and J.Kuhlmann (2009).
Mapping the isoprenoid binding pocket of PDEdelta by a semisynthetic, photoactivatable N-Ras lipoprotein.
  Chembiochem, 10, 98.  
19733088 M.Hattori, Y.Jin, H.Nishimasu, Y.Tanaka, M.Mochizuki, T.Uchiumi, R.Ishitani, K.Ito, and O.Nureki (2009).
Structural basis of novel interactions between the small-GTPase and GDI-like domains in prokaryotic FeoB iron transporter.
  Structure, 17, 1345-1355.
PDB codes: 3a1s 3a1t 3a1u 3a1v 3a1w
17901255 A.Schmandke, A.Schmandke, and S.M.Strittmatter (2007).
ROCK and Rho: biochemistry and neuronal functions of Rho-associated protein kinases.
  Neuroscientist, 13, 454-469.  
17452788 G.Prehna, and C.E.Stebbins (2007).
A Rac1-GDP trimer complex binds zinc with tetrahedral and octahedral coordination, displacing magnesium.
  Acta Crystallogr D Biol Crystallogr, 63, 628-635.
PDB code: 2p2l
17245428 J.P.ten Klooster, I.Leeuwen, N.Scheres, E.C.Anthony, and P.L.Hordijk (2007).
Rac1-induced cell migration requires membrane recruitment of the nuclear oncogene SET.
  EMBO J, 26, 336-345.  
17622327 S.Ihalainen, R.Soliymani, E.Iivanainen, K.Mykkänen, A.Sainio, M.Pöyhönen, K.Elenius, H.Järveläinen, M.Viitanen, H.Kalimo, and M.Baumann (2007).
Proteome analysis of cultivated vascular smooth muscle cells from a CADASIL patient.
  Mol Med, 13, 305-314.  
16959567 G.Prehna, M.I.Ivanov, J.B.Bliska, and C.E.Stebbins (2006).
Yersinia virulence depends on mimicry of host Rho-family nucleotide dissociation inhibitors.
  Cell, 126, 869-880.
PDB codes: 2h7o 2h7v
16492808 J.P.ten Klooster, Z.M.Jaffer, J.Chernoff, and P.L.Hordijk (2006).
Targeting and activation of Rac1 are mediated by the exchange factor beta-Pix.
  J Cell Biol, 172, 759-769.  
16597700 K.Moissoglu, B.M.Slepchenko, N.Meller, A.F.Horwitz, and M.A.Schwartz (2006).
In vivo dynamics of Rac-membrane interactions.
  Mol Biol Cell, 17, 2770-2779.  
16702219 Y.Ugolev, S.Molshanski-Mor, C.Weinbaum, and E.Pick (2006).
Liposomes comprising anionic but not neutral phospholipids cause dissociation of Rac(1 or 2) x RhoGDI complexes and support amphiphile-independent NADPH oxidase activation by such complexes.
  J Biol Chem, 281, 19204-19219.  
16307476 A.Eberth, R.Dvorsky, C.F.Becker, A.Beste, R.S.Goody, and M.R.Ahmadian (2005).
Monitoring the real-time kinetics of the hydrolysis reaction of guanine nucleotide-binding proteins.
  Biol Chem, 386, 1105-1114.  
15921909 C.DerMardirossian, and G.M.Bokoch (2005).
GDIs: central regulatory molecules in Rho GTPase activation.
  Trends Cell Biol, 15, 356-363.  
15513926 E.Dransart, A.Morin, J.Cherfils, and B.Olofsson (2005).
Uncoupling of inhibitory and shuttling functions of rho GDP dissociation inhibitors.
  J Biol Chem, 280, 4674-4683.  
16190977 E.Dransart, B.Olofsson, and J.Cherfils (2005).
RhoGDIs revisited: novel roles in Rho regulation.
  Traffic, 6, 957-966.  
15596440 P.Moskwa, M.H.Paclet, M.C.Dagher, and E.Ligeti (2005).
Autoinhibition of p50 Rho GTPase-activating protein (GAP) is released by prenylated small GTPases.
  J Biol Chem, 280, 6716-6720.  
16355224 R.J.Carol, S.Takeda, P.Linstead, M.C.Durrant, H.Kakesova, P.Derbyshire, S.Drea, V.Zarsky, and L.Dolan (2005).
A RhoGDP dissociation inhibitor spatially regulates growth in root hair cells.
  Nature, 438, 1013-1016.  
15383551 B.Mesmin, K.Robbe, B.Geny, F.Luton, G.Brandolin, M.R.Popoff, and B.Antonny (2004).
A phosphatidylserine-binding site in the cytosolic fragment of Clostridium sordellii lethal toxin facilitates glucosylation of membrane-bound Rac and is required for cytotoxicity.
  J Biol Chem, 279, 49876-49882.  
14625275 D.Fiegen, L.C.Haeusler, L.Blumenstein, U.Herbrand, R.Dvorsky, I.R.Vetter, and M.R.Ahmadian (2004).
Alternative splicing of Rac1 generates Rac1b, a self-activating GTPase.
  J Biol Chem, 279, 4743-4749.
PDB codes: 1ryf 1ryh
15143066 M.Pop, K.Aktories, and G.Schmidt (2004).
Isotype-specific degradation of Rac activated by the cytotoxic necrotizing factor 1.
  J Biol Chem, 279, 35840-35848.  
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.  
12454455 A.Mateja, Y.Devedjiev, D.Krowarsch, K.Longenecker, Z.Dauter, J.Otlewski, and Z.S.Derewenda (2002).
The impact of Glu-->Ala and Glu-->Asp mutations on the crystallization properties of RhoGDI: the structure of RhoGDI at 1.3 A resolution.
  Acta Crystallogr D Biol Crystallogr, 58, 1983-1991.
PDB code: 1kmt
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
11967128 N.Brunet, A.Morin, and B.Olofsson (2002).
RhoGDI-3 regulates RhoG and targets this protein to the Golgi complex through its unique N-terminal domain.
  Traffic, 3, 342-357.  
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.  
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.