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Signaling protein PDB id
1shz
Jmol
Contents
Protein chains
326 a.a. *
196 a.a. *
188 a.a. *
Ligands
ALF-GDP ×2
Metals
_MG ×2
Waters ×84
* Residue conservation analysis
PDB id:
1shz
Name: Signaling protein
Title: Crystal structure of the p115rhogef rgrgs domain in a complex with galpha(13):galpha(i1) chimera
Structure: Guanine nucleotide-binding protein galpha(13) :galpha(i1) chimera. Chain: a, d. Fragment: residues 21-47, 185-210, 213-230, 240-353 of galpha(i1) and residues 64-207, 234-235, 254-262 of galpha(13). Engineered: yes. Rho guanine nucleotide exchange factor 1. Chain: c, f.
Source: Mus musculus, rattus norvegicus. House mouse, norway rat. Organism_taxid: 10090,10116. Strain: ,. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606.
Biol. unit: Tetramer (from PQS)
Resolution:
2.85Å     R-factor:   0.229     R-free:   0.297
Authors: Z.Chen,W.D.Singer,P.C.Sternweis,S.R.Sprang
Key ref:
Z.Chen et al. (2005). Structure of the p115RhoGEF rgRGS domain-Galpha13/i1 chimera complex suggests convergent evolution of a GTPase activator. Nat Struct Mol Biol, 12, 191-197. PubMed id: 15665872 DOI: 10.1038/nsmb888
Date:
26-Feb-04     Release date:   18-Jan-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P10824  (GNAI1_RAT) -  Guanine nucleotide-binding protein G(i) subunit alpha-1
Seq:
Struc: 		354 a.a.
326 a.a.*
Protein chains
Pfam   ArchSchema ?
P27601  (GNA13_MOUSE) -  Guanine nucleotide-binding protein subunit alpha-13
Seq:
Struc: 		377 a.a.
326 a.a.*
Protein chain
Pfam   ArchSchema ?
Q92888  (ARHG1_HUMAN) -  Rho guanine nucleotide exchange factor 1
Seq:
Struc: 		 
Seq:
Struc: 		912 a.a.
196 a.a.
Protein chain
Pfam   ArchSchema ?
Q92888  (ARHG1_HUMAN) -  Rho guanine nucleotide exchange factor 1
Seq:
Struc: 		 
Seq:
Struc: 		912 a.a.
188 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 189 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   13 terms 
  Biological process     termination of G-protein coupled receptor signaling pathway   7 terms 
  Biochemical function     nucleotide binding     9 terms  

 

 
DOI no: 10.1038/nsmb888 Nat Struct Mol Biol 12:191-197 (2005)
PubMed id: 15665872  
 
 
Structure of the p115RhoGEF rgRGS domain-Galpha13/i1 chimera complex suggests convergent evolution of a GTPase activator.
Z.Chen, W.D.Singer, P.C.Sternweis, S.R.Sprang.
 
  ABSTRACT  
 
p115RhoGEF, a guanine nucleotide exchange factor (GEF) for Rho GTPase, is also a GTPase-activating protein (GAP) for G12 and G13 heterotrimeric Galpha subunits. The GAP function of p115RhoGEF resides within the N-terminal region of p115RhoGEF (the rgRGS domain), which includes a module that is structurally similar to RGS (regulators of G-protein signaling) domains. We present here the crystal structure of the rgRGS domain of p115RhoGEF in complex with a chimera of Galpha13 and Galphai1. Two distinct surfaces of rgRGS interact with Galpha. The N-terminal betaN-alphaN hairpin of rgRGS, rather than its RGS module, forms intimate contacts with the catalytic site of Galpha. The interface between the RGS module of rgRGS and Galpha is similar to that of a Galpha-effector complex, suggesting a role for the rgRGS domain in the stimulation of the GEF activity of p115RhoGEF by Galpha13.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Electrostatic potentials of the rgRGS -G 13/i-5 complex. Ribbon diagrams depicting the tertiary structures (top row, same coloring scheme as in Fig. 2a) and the corresponding solvent-accessible surfaces (bottom row) of the rgRGS domain (left), the complex (center) and G 13/i-5 (right). Solvent-accessible surfaces are colored according to electrostatic potential in the range of -10 kT (red) to +10 kT (blue), where k is the Boltzmann's constant and T is temperature (K). The complex is rotated 90° about the horizontal with respect to the view shown in Figure 2a. The rgRGS domain and G 13/i-5 are rotated as indicated. 		Figure 5.
Figure 5. The interface between the RGS subdomain of rgRGS and G 13/i-5. (a) Ribbon diagram showing interactions between the RGS subdomain (including the conserved RGS box) and switch II and the 3 helix of G 13/i-5. (b) Ribbon diagrams showing effector-binding sites of rgRGS -G 13/i-5, AC -G s31 and PDE -G t/i1 (ref. 14). AC is gold (IIC[2]) or red (VC[1]), and PDE is gold.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2005, 12, 191-197) copyright 2005.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21064165 Z.Chen, L.Guo, S.R.Sprang, and P.C.Sternweis (2011).
Modulation of a GEF switch: autoinhibition of the intrinsic guanine nucleotide exchange activity of p115-RhoGEF.
  Protein Sci, 20, 107-117.  
20976244 B.R.Temple, C.D.Jones, and A.M.Jones (2010).
Evolution of a signaling nexus constrained by protein interfaces and conformational States.
  PLoS Comput Biol, 6, e1000962.  
20966218 G.L.Waldo, T.K.Ricks, S.N.Hicks, M.L.Cheever, T.Kawano, K.Tsuboi, X.Wang, C.Montell, T.Kozasa, J.Sondek, and T.K.Harden (2010).
Kinetic scaffolding mediated by a phospholipase C-beta and Gq signaling complex.
  Science, 330, 974-980.
PDB code: 3ohm
  20877687 G.Yang, R.Lucas, R.Caldwell, L.Yao, M.J.Romero, and R.W.Caldwell (2010).
Novel mechanisms of endothelial dysfunction in diabetes.
  J Cardiovasc Dis Res, 1, 59-63.  
19880753 M.Aittaleb, C.A.Boguth, and J.J.Tesmer (2010).
Structure and function of heterotrimeric G protein-regulated Rho guanine nucleotide exchange factors.
  Mol Pharmacol, 77, 111-125.  
19760664 H.E.Hamm, S.M.Meier, G.Liao, and A.M.Preininger (2009).
Trp fluorescence reveals an activation-dependent cation-pi interaction in the Switch II region of Galphai proteins.
  Protein Sci, 18, 2326-2335.  
19560536 M.Aittaleb, G.Gao, C.R.Evelyn, R.R.Neubig, and J.J.Tesmer (2009).
A conserved hydrophobic surface of the LARG pleckstrin homology domain is critical for RhoA activation in cells.
  Cell Signal, 21, 1569-1578.  
19460155 M.Zheng, T.Cierpicki, K.Momotani, M.V.Artamonov, U.Derewenda, J.H.Bushweller, A.V.Somlyo, and Z.S.Derewenda (2009).
On the mechanism of autoinhibition of the RhoA-specific nucleotide exchange factor PDZRhoGEF.
  BMC Struct Biol, 9, 36.  
19074425 N.Suzuki, K.Tsumoto, N.Hajicek, K.Daigo, R.Tokita, S.Minami, T.Kodama, T.Hamakubo, and T.Kozasa (2009).
Activation of Leukemia-associated RhoGEF by G{alpha}13 with Significant Conformational Rearrangements in the Interface.
  J Biol Chem, 284, 5000-5009.  
19212140 N.Suzuki, N.Hajicek, and T.Kozasa (2009).
Regulation and physiological functions of G12/13-mediated signaling pathways.
  Neurosignals, 17, 55-70.  
19249348 R.Bhattacharyya, J.Banerjee, K.Khalili, and P.B.Wedegaertner (2009).
Differences in Galpha12- and Galpha13-mediated plasma membrane recruitment of p115-RhoGEF.
  Cell Signal, 21, 996.  
18320579 B.H.Meyer, F.Freuler, D.Guerini, and S.Siehler (2008).
Reversible translocation of p115-RhoGEF by G(12/13)-coupled receptors.
  J Cell Biochem, 104, 1660-1670.  
18940599 M.B.Hamaneh, and M.Buck (2008).
Tripping a switch: PDZRhoGEF rgRGS-bound Galpha13.
  Structure, 16, 1439-1441.  
18434541 M.Soundararajan, F.S.Willard, A.J.Kimple, A.P.Turnbull, L.J.Ball, G.A.Schoch, C.Gileadi, O.Y.Fedorov, E.F.Dowler, V.A.Higman, S.Q.Hutsell, M.Sundström, D.A.Doyle, and D.P.Siderovski (2008).
Structural diversity in the RGS domain and its interaction with heterotrimeric G protein alpha-subunits.
  Proc Natl Acad Sci U S A, 105, 6457-6462.
PDB codes: 1zv4 2a72 2af0 2bt2 2bv1 2es0 2gtp 2i59 2ihb 2ihd 2ik8 2jm5 2jnu 2ode 2owi
18329041 R.J.Austin, W.W.Ja, and R.W.Roberts (2008).
Evolution of class-specific peptides targeting a hot spot of the Galphas subunit.
  J Mol Biol, 377, 1406-1418.  
18940608 Z.Chen, W.D.Singer, S.M.Danesh, P.C.Sternweis, and S.R.Sprang (2008).
Recognition of the activated states of Galpha13 by the rgRGS domain of PDZRhoGEF.
  Structure, 16, 1532-1543.
PDB codes: 3cx6 3cx7 3cx8
18096806 S.Lutz, A.Shankaranarayanan, C.Coco, M.Ridilla, M.R.Nance, C.Vettel, D.Baltus, C.R.Evelyn, R.R.Neubig, T.Wieland, and J.J.Tesmer (2007).
Structure of Galphaq-p63RhoGEF-RhoA complex reveals a pathway for the activation of RhoA by GPCRs.
  Science, 318, 1923-1927.
PDB code: 2rgn
17463080 W.M.Oldham, N.Van Eps, A.M.Preininger, W.L.Hubbell, and H.E.Hamm (2007).
Mapping allosteric connections from the receptor to the nucleotide-binding pocket of heterotrimeric G proteins.
  Proc Natl Acad Sci U S A, 104, 7927-7932.  
16954208 A.Oleksy, Ć..OpaliƄski, U.Derewenda, Z.S.Derewenda, and J.Otlewski (2006).
The molecular basis of RhoA specificity in the guanine nucleotide exchange factor PDZ-RhoGEF.
  J Biol Chem, 281, 32891-32897.  
16388592 B.Kreutz, D.M.Yau, M.R.Nance, S.Tanabe, J.J.Tesmer, and T.Kozasa (2006).
A new approach to producing functional G alpha subunits yields the activated and deactivated structures of G alpha(12/13) proteins.
  Biochemistry, 45, 167-174.
PDB codes: 1zca 1zcb
16981699 C.A.Johnston, E.S.Lobanova, A.S.Shavkunov, J.Low, J.K.Ramer, R.Blaesius, Z.Fredericks, F.S.Willard, B.Kuhlman, V.Y.Arshavsky, and D.P.Siderovski (2006).
Minimal determinants for binding activated G alpha from the structure of a G alpha(i1)-peptide dimer.
  Biochemistry, 45, 11390-11400.
PDB code: 2g83
16613860 D.T.Lodowski, V.M.Tesmer, J.L.Benovic, and J.J.Tesmer (2006).
The structure of G protein-coupled receptor kinase (GRK)-6 defines a second lineage of GRKs.
  J Biol Chem, 281, 16785-16793.
PDB code: 2acx
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
16183138 E.Kostenis, M.Waelbroeck, and G.Milligan (2005).
Techniques: promiscuous Galpha proteins in basic research and drug discovery.
  Trends Pharmacol Sci, 26, 595-602.  
16243026 T.M.Wilkie, and L.Kinch (2005).
New roles for Galpha and RGS proteins: communication continues despite pulling sisters apart.
  Curr Biol, 15, R843-R854.  
16339447 V.M.Tesmer, T.Kawano, A.Shankaranarayanan, T.Kozasa, and J.J.Tesmer (2005).
Snapshot of activated G proteins at the membrane: the Galphaq-GRK2-Gbetagamma complex.
  Science, 310, 1686-1690.
PDB code: 2bcj
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.