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PDBsum entry 1a0r
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protein ligands Protein-protein interface(s) links
Complex (transducer/transduction) PDB id
1a0r

 

 

 

 

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Contents
Protein chains
340 a.a. *
65 a.a. *
188 a.a. *
Ligands
FAR
Waters ×21
* Residue conservation analysis
PDB id:
1a0r
Name: Complex (transducer/transduction)
Title: Heterotrimeric complex of phosducin/transducin beta-gamma
Structure: Transducin (beta subunit). Chain: b. Synonym: gt beta. Other_details: protein complex was isolated from native source (bovine retina). Gamma subunit is farnesylated at position cys 71. Transducin (gamma subunit). Chain: g. Synonym: gt gamma. Other_details: protein complex was isolated from native source
Source: Bos taurus. Cattle. Organism_taxid: 9913. Organ: eye. Tissue: retina. Cellular_location: rod outer segments. Other_details: purified from bovine rod outer segment. Other_details: purified from bovine rod outer segment in complex with transducin beta-gamma subunit
Biol. unit: Trimer (from PQS)
Resolution:
2.80Å     R-factor:   0.228     R-free:   0.264
Authors: A.Loew,Y.-K.Ho,T.L.Blundell,B.Bax
Key ref:
A.Loew et al. (1998). Phosducin induces a structural change in transducin beta gamma. Structure, 6, 1007-1019. PubMed id: 9739091 DOI: 10.1016/S0969-2126(98)00102-6
Date:
05-Dec-97     Release date:   30-Dec-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P62871  (GBB1_BOVIN) -  Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 from Bos taurus
Seq:
Struc: 		340 a.a.
339 a.a.*
Protein chain
Pfam   ArchSchema ?
P02698  (GBG1_BOVIN) -  Guanine nucleotide-binding protein G(T) subunit gamma-T1 from Bos taurus
Seq:
Struc: 		74 a.a.
65 a.a.
Protein chain
Pfam   ArchSchema ?
P19632  (PHOS_BOVIN) -  Phosducin from Bos taurus
Seq:
Struc: 		245 a.a.
188 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 

 
DOI no: 10.1016/S0969-2126(98)00102-6 Structure 6:1007-1019 (1998)
PubMed id: 9739091  
 
 
Phosducin induces a structural change in transducin beta gamma.
A.Loew, Y.K.Ho, T.Blundell, B.Bax.
 
  ABSTRACT  
 
BACKGROUND: Phosducin binds tightly to the beta gamma subunits (Gt beta gamma) of the heterotrimeric G protein transducin, preventing Gt beta gamma reassociation with Gt alpha-GDP and thereby inhibiting the G-protein cycle. Phosducin-like proteins appear to be widely distributed and may play important roles in regulating many heterotrimeric G-protein signaling pathways. RESULTS: The 2.8 A crystal structure of a complex of bovine retinal phosducin with Gt beta gamma shows how the two domains of phosducin cover one side and the top of the seven-bladed beta propeller of Gt beta gamma. The binding of phosducin induces a distinct structural change in the beta propeller of Gt beta gamma, such that a small cavity opens up between blades 6 and 7. Electron density in this cavity has been assigned to the farnesyl moiety of the gamma subunit. CONCLUSIONS: beta gamma subunits of heterotrimeric G proteins can exist in two distinct conformations. In the R (relaxed) state, corresponding to the structure of the free beta gamma or the structure of beta gamma in the alpha beta gamma heterotrimer, the hydrophobic farnesyl moiety of the gamma subunit is exposed, thereby mediating membrane association. In the T (tense) state, as observed in the phosducin-Gt beta gamma structure, the farnesyl moiety of the gamma subunit is effectively buried in the cavity formed between blades 6 and 7 of the beta subunit. Binding of phosducin to Gt beta gamma induces the formation of this cavity, resulting in a switch from the R to the T conformation. This sequesters beta gamma from the membrane to the cytosol and turns off the signal-transduction cascade. Regulation of this membrane association/dissociation switch of Gt beta gamma by phosducin may be a general mechanism for attenuation of G protein coupled signal transduction cascades.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Stereo diagrams [41 and 42] of SIGMAA weighted 2F[o]-F[c] maps from round 13 of the refinement. The structure was refined with either (a) a farnesyl (in green) in the pocket (map contoured at 1s) or (b) the water structure (red spheres) from Gaudet et al. [12] (PDB code 2TRC; contoured at 0.8s). The refinement was carried out with the program X-PLOR [33], and included a bulk solvent correction as well as conventional positional refinement. Note that in (b) the waters have moved very little from their starting positions and make good hydrogen bonds with surrounding residues. Only hydrogen bonds between protein residues are shown (dashed lines).
 
  The above figure is reprinted by permission from Cell Press: Structure (1998, 6, 1007-1019) copyright 1998.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21064128 M.S.Park, A.V.Smrcka, and H.A.Stern (2011).
Conformational flexibility and binding interactions of the G protein βγ heterodimer.
  Proteins, 79, 518-527.  
20018744 A.V.Smrcka, N.Kichik, T.Tarragó, M.Burroughs, M.S.Park, N.K.Itoga, H.A.Stern, B.M.Willardson, and E.Giralt (2010).
NMR analysis of G-protein betagamma subunit complexes reveals a dynamic G(alpha)-Gbetagamma subunit interface and multiple protein recognition modes.
  Proc Natl Acad Sci U S A, 107, 639-644.  
20581844 S.Orlicky, X.Tang, V.Neduva, N.Elowe, E.D.Brown, F.Sicheri, and M.Tyers (2010).
An allosteric inhibitor of substrate recognition by the SCF(Cdc4) ubiquitin ligase.
  Nat Biotechnol, 28, 733-737.
PDB code: 3mks
19646992 E.J.Friedman, B.R.Temple, S.N.Hicks, J.Sondek, C.D.Jones, and A.M.Jones (2009).
Prediction of protein-protein interfaces on G-protein beta subunits reveals a novel phospholipase C beta2 binding domain.
  J Mol Biol, 392, 1044-1054.  
19403526 M.L.Guzmán-Hernández, A.Vázquez-Macías, J.Carretero-Ortega, R.Hernández-García, A.García-Regalado, I.Hernández-Negrete, G.Reyes-Cruz, J.S.Gutkind, and J.Vázquez-Prado (2009).
Differential Inhibitor of G{beta}{gamma} Signaling to AKT and ERK Derived from Phosducin-like Protein: EFFECT ON SPHINGOSINE 1-PHOSPHATE-INDUCED ENDOTHELIAL CELL MIGRATION AND IN VITRO ANGIOGENESIS.
  J Biol Chem, 284, 18334-18346.  
19212142 W.E.McIntire (2009).
Structural determinants involved in the formation and activation of G protein betagamma dimers.
  Neurosignals, 17, 82-99.  
  19193988 X.Lou, R.Bao, C.Z.Zhou, and Y.Chen (2009).
Structure of the thioredoxin-fold domain of human phosducin-like protein 2.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 67-70.
PDB code: 3evi
18488142 A.V.Smrcka (2008).
G protein betagamma subunits: central mediators of G protein-coupled receptor signaling.
  Cell Mol Life Sci, 65, 2191-2214.  
18367617 E.S.Lobanova, S.Finkelstein, R.Herrmann, Y.M.Chen, C.Kessler, N.A.Michaud, L.H.Trieu, K.J.Strissel, M.E.Burns, and V.Y.Arshavsky (2008).
Transducin gamma-subunit sets expression levels of alpha- and beta-subunits and is crucial for rod viability.
  J Neurosci, 28, 3510-3520.  
18636747 M.Katadae, K.Hagiwara, A.Wada, M.Ito, M.Umeda, P.J.Casey, and Y.Fukada (2008).
Interacting targets of the farnesyl of transducin gamma-subunit.
  Biochemistry, 47, 8424-8433.  
18782760 M.Kosloff, E.Alexov, V.Y.Arshavsky, and B.Honig (2008).
Electrostatic and Lipid Anchor Contributions to the Interaction of Transducin with Membranes: MECHANISTIC IMPLICATIONS FOR ACTIVATION AND TRANSLOCATION.
  J Biol Chem, 283, 31197-31207.  
18425604 N.O.Artemyev (2008).
Light-dependent compartmentalization of transducin in rod photoreceptors.
  Mol Neurobiol, 37, 44-51.  
18379987 V.Z.Slepak, and J.B.Hurley (2008).
Mechanism of light-induced translocation of arrestin and transducin in photoreceptors: interaction-restricted diffusion.
  IUBMB Life, 60, 2-9.  
17658730 B.M.Willardson, and A.C.Howlett (2007).
Function of phosducin-like proteins in G protein signaling and chaperone-assisted protein folding.
  Cell Signal, 19, 2417-2427.  
17201690 B.R.Temple, and A.M.Jones (2007).
The plant heterotrimeric G-protein complex.
  Annu Rev Plant Biol, 58, 249-266.  
16517125 M.Akgoz, V.Kalyanaraman, and N.Gautam (2006).
G protein betagamma complex translocation from plasma membrane to Golgi complex is influenced by receptor gamma subunit interaction.
  Cell Signal, 18, 1758-1768.  
15644329 D.K.Wilson, D.Cerna, and E.Chew (2005).
The 1.1-angstrom structure of the spindle checkpoint protein Bub3p reveals functional regions.
  J Biol Chem, 280, 13944-13951.
PDB code: 1yfq
16135826 J.C.Knol, R.Engel, M.Blaauw, A.J.Visser, and P.J.van Haastert (2005).
The phosducin-like protein PhLP1 is essential for G{beta}{gamma} dimer formation in Dictyostelium discoideum.
  Mol Cell Biol, 25, 8393-8400.  
15152089 A.Y.Madrona, and D.K.Wilson (2004).
The structure of Ski8p, a protein regulating mRNA degradation: Implications for WD protein structure.
  Protein Sci, 13, 1557-1565.
PDB code: 1sq9
14973130 M.Sokolov, K.J.Strissel, I.B.Leskov, N.A.Michaud, V.I.Govardovskii, and V.Y.Arshavsky (2004).
Phosducin facilitates light-driven transducin translocation in rod photoreceptors. Evidence from the phosducin knockout mouse.
  J Biol Chem, 279, 19149-19156.  
15173184 Z.Zhang, T.J.Melia, F.He, C.Yuan, A.McGough, M.F.Schmid, and T.G.Wensel (2004).
How a G protein binds a membrane.
  J Biol Chem, 279, 33937-33945.  
12764189 D.T.Lodowski, J.A.Pitcher, W.D.Capel, R.J.Lefkowitz, and J.J.Tesmer (2003).
Keeping G proteins at bay: a complex between G protein-coupled receptor kinase 2 and Gbetagamma.
  Science, 300, 1256-1262.
PDB code: 1omw
12649269 F.Goubaeva, M.Ghosh, S.Malik, J.Yang, P.M.Hinkle, K.K.Griendling, R.R.Neubig, and A.V.Smrcka (2003).
Stimulation of cellular signaling and G protein subunit dissociation by G protein betagamma subunit-binding peptides.
  J Biol Chem, 278, 19634-19641.  
14609943 J.S.Taylor, T.S.Reid, K.L.Terry, P.J.Casey, and L.S.Beese (2003).
Structure of mammalian protein geranylgeranyltransferase type-I.
  EMBO J, 22, 5963-5974.
PDB codes: 1n4p 1n4q 1n4r 1n4s
13678959 K.D.Ridge, N.G.Abdulaev, M.Sousa, and K.Palczewski (2003).
Phototransduction: crystal clear.
  Trends Biochem Sci, 28, 479-487.  
14517243 M.Blaauw, J.C.Knol, A.Kortholt, J.Roelofs, Ruchira, M.Postma, A.J.Visser, and P.J.van Haastert (2003).
Phosducin-like proteins in Dictyostelium discoideum: implications for the phosducin family of proteins.
  EMBO J, 22, 5047-5057.  
12881533 M.Ghosh, Y.K.Peterson, S.M.Lanier, and A.V.Smrcka (2003).
Receptor- and nucleotide exchange-independent mechanisms for promoting G protein subunit dissociation.
  J Biol Chem, 278, 34747-34750.  
12057191 L.M.Pickles, S.M.Roe, E.J.Hemingway, S.Stifani, and L.H.Pearl (2002).
Crystal structure of the C-terminal WD40 repeat domain of the human Groucho/TLE1 transcriptional corepressor.
  Structure, 10, 751-761.
PDB code: 1gxr
11914377 M.Akgoz, I.Azpiazu, V.Kalyanaraman, and N.Gautam (2002).
Role of the G protein gamma subunit in beta gamma complex modulation of phospholipase Cbeta function.
  J Biol Chem, 277, 19573-19578.  
11988478 T.P.Sakmar, S.T.Menon, E.P.Marin, and E.S.Awad (2002).
Rhodopsin: insights from recent structural studies.
  Annu Rev Biophys Biomol Struct, 31, 443-484.  
11179221 J.K.Scott, S.F.Huang, B.P.Gangadhar, G.M.Samoriski, P.Clapp, R.A.Gross, R.Taussig, and A.V.Smrcka (2001).
Evidence that a protein-protein interaction 'hot spot' on heterotrimeric G protein betagamma subunits is used for recognition of a subclass of effectors.
  EMBO J, 20, 767-776.  
10922079 C.S.Myung, and J.C.Garrison (2000).
Role of C-terminal domains of the G protein beta subunit in the activation of effectors.
  Proc Natl Acad Sci U S A, 97, 9311-9316.  
10744734 C.V.Carman, L.S.Barak, C.Chen, L.Y.Liu-Chen, J.J.Onorato, S.P.Kennedy, M.G.Caron, and J.L.Benovic (2000).
Mutational analysis of Gbetagamma and phospholipid interaction with G protein-coupled receptor kinase 2.
  J Biol Chem, 275, 10443-10452.  
10652348 T.J.Melia, J.A.Malinski, F.He, and T.G.Wensel (2000).
Enhancement of phototransduction protein interactions by lipid surfaces.
  J Biol Chem, 275, 3535-3542.  
11076027 T.L.Blundell, D.F.Burke, D.Chirgadze, V.Dhanaraj, M.Hyvönen, C.A.Innis, E.Parisini, L.Pellegrini, M.Sayed, and B.L.Sibanda (2000).
Protein-protein interactions in receptor activation and intracellular signalling.
  Biol Chem, 381, 955-959.  
10360181 R.Gaudet, J.R.Savage, J.N.McLaughlin, B.M.Willardson, and P.B.Sigler (1999).
A molecular mechanism for the phosphorylation-dependent regulation of heterotrimeric G proteins by phosducin.
  Mol Cell, 3, 649-660.
PDB codes: 1b9x 1b9y
10322433 T.F.Smith, C.Gaitatzes, K.Saxena, and E.J.Neer (1999).
The WD repeat: a common architecture for diverse functions.
  Trends Biochem Sci, 24, 181-185.  
10607670 V.Fülöp, and D.T.Jones (1999).
Beta propellers: structural rigidity and functional diversity.
  Curr Opin Struct Biol, 9, 715-721.  
9790522 S.R.Sprang, and D.E.Coleman (1998).
Invasion of the nucleotide snatchers: structural insights into the mechanism of G protein GEFs.
  Cell, 95, 155-158.  
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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