spacer
spacer
Go to PDB code: 
protein ligands links
Signal transduction protein PDB id
1gdd
Jmol
Contents
Protein chain
324 a.a. *
Ligands
SO4
GDP
Waters ×70
* Residue conservation analysis
PDB id:
1gdd
Name: Signal transduction protein
Title: Tertiary and quaternary structural changes in gia1 induced by gtp hydrolysis
Structure: Gi alpha 1. Chain: a. Synonym: gia1, guanine nucleotide-binding protein g(i), alpha-1 subunit. Engineered: yes. Other_details: inactive form
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.20Å     R-factor:   0.214     R-free:   0.291
Authors: M.B.Mixon,S.R.Sprang
Key ref: M.B.Mixon et al. (1995). Tertiary and quaternary structural changes in Gi alpha 1 induced by GTP hydrolysis. Science, 270, 954-960. PubMed id: 7481799 DOI: 10.1126/science.270.5238.954
Date:
25-Jul-95     Release date:   27-Nov-95    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P10824  (GNAI1_RAT) -  Guanine nucleotide-binding protein G(i) subunit alpha-1
Seq:
Struc: 		354 a.a.
324 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   13 terms 
  Biological process     cell cycle   6 terms 
  Biochemical function     nucleotide binding     8 terms  

 

 
DOI no: 10.1126/science.270.5238.954 Science 270:954-960 (1995)
PubMed id: 7481799  
 
 
Tertiary and quaternary structural changes in Gi alpha 1 induced by GTP hydrolysis.
M.B.Mixon, E.Lee, D.E.Coleman, A.M.Berghuis, A.G.Gilman, S.R.Sprang.
 
  ABSTRACT  
 
Crystallographic analysis of 2.2 angstrom resolution shows that guanosine triphosphate (GTP) hydrolysis triggers conformational changes in the heterotrimeric G-protein alpha subunit, Gi alpha 1. The switch II and switch III segments become disordered, and linker II connecting the Ras and alpha helical domains moves, thus altering the structures of potential effector and beta gamma binding regions. Contacts between the alpha-helical and Ras domains are weakened, possibly facilitating the release of guanosine diphosphate (GDP). The amino and carboxyl termini, which contain receptor and beta gamma binding determinants, are disordered in the complex with GTP, but are organized into a compact microdomain on GDP hydrolysis. The amino terminus also forms extensive quaternary contacts with neighboring alpha subunits in the lattice, suggesting that multimers of alpha subunits or heterotrimers may play a role in signal transduction.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20639466 A.Nishimura, K.Kitano, J.Takasaki, M.Taniguchi, N.Mizuno, K.Tago, T.Hakoshima, and H.Itoh (2010).
Structural basis for the specific inhibition of heterotrimeric Gq protein by a small molecule.
  Proc Natl Acad Sci U S A, 107, 13666-13671.
PDB code: 3ah8
20139237 F.D.Ivey, F.X.Taglia, F.Yang, M.M.Lander, D.A.Kelly, and C.S.Hoffman (2010).
Activated alleles of the Schizosaccharomyces pombe gpa2+ Galpha gene identify residues involved in GDP-GTP exchange.
  Eukaryot Cell, 9, 626-633.  
20520658 J.J.Tesmer (2010).
The quest to understand heterotrimeric G protein signaling.
  Nat Struct Mol Biol, 17, 650-652.  
20351284 N.A.Lambert, C.A.Johnston, S.D.Cappell, S.Kuravi, A.J.Kimple, F.S.Willard, and D.P.Siderovski (2010).
Regulators of G-protein signaling accelerate GPCR signaling kinetics and govern sensitivity solely by accelerating GTPase activity.
  Proc Natl Acad Sci U S A, 107, 7066-7071.  
19222191 A.M.Preininger, M.A.Funk, W.M.Oldham, S.M.Meier, C.A.Johnston, S.Adhikary, A.J.Kimple, D.P.Siderovski, H.E.Hamm, and T.M.Iverson (2009).
Helix dipole movement and conformational variability contribute to allosteric GDP release in Galphai subunits.
  Biochemistry, 48, 2630-2642.
PDB code: 3d7m
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.  
18771287 A.M.Preininger, J.Parello, S.M.Meier, G.Liao, and H.E.Hamm (2008).
Receptor-mediated changes at the myristoylated amino terminus of Galpha(il) proteins.
  Biochemistry, 47, 10281-10293.  
18488142 A.V.Smrcka (2008).
G protein betagamma subunits: central mediators of G protein-coupled receptor signaling.
  Cell Mol Life Sci, 65, 2191-2214.  
18519563 C.A.Johnston, K.Afshar, J.T.Snyder, G.G.Tall, P.Gönczy, D.P.Siderovski, and F.S.Willard (2008).
Structural determinants underlying the temperature-sensitive nature of a Galpha mutant in asymmetric cell division of Caenorhabditis elegans.
  J Biol Chem, 283, 21550-21558.
PDB code: 2ebc
18541531 C.J.Thomas, G.G.Tall, A.Adhikari, and S.R.Sprang (2008).
Ric-8A catalyzes guanine nucleotide exchange on G alphai1 bound to the GPR/GoLoco exchange inhibitor AGS3.
  J Biol Chem, 283, 23150-23160.  
18249008 E.McCusker, and A.S.Robinson (2008).
Refolding of G protein alpha subunits from inclusion bodies expressed in Escherichia coli.
  Protein Expr Purif, 58, 342-355.  
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.  
18043707 W.M.Oldham, and H.E.Hamm (2008).
Heterotrimeric G protein activation by G-protein-coupled receptors.
  Nat Rev Mol Cell Biol, 9, 60-71.  
17588669 L.S.Weinstein, T.Xie, Q.H.Zhang, and M.Chen (2007).
Studies of the regulation and function of the Gs alpha gene Gnas using gene targeting technology.
  Pharmacol Ther, 115, 271-291.  
17651824 S.L.Parker, M.S.Parker, F.R.Sallee, and A.Balasubramaniam (2007).
Oligomerization of neuropeptide Y (NPY) Y2 receptors in CHO cells depends on functional pertussis toxin-sensitive G-proteins.
  Regul Pept, 144, 72-81.  
  17277460 T.Morikawa, A.Muroya, Y.Nakajima, T.Tanaka, K.Hirai, S.Sugio, K.Wakamatsu, and T.Kohno (2007).
Crystallization and preliminary X-ray crystallographic analysis of the receptor-uncoupled mutant of Galphai1.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 139-141.  
17200862 T.Wieland (2007).
Interaction of nucleoside diphosphate kinase B with heterotrimeric G protein betagamma dimers: consequences on G protein activation and stability.
  Naunyn Schmiedebergs Arch Pharmacol, 374, 373-383.  
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.  
16698293 C.Hill, A.Goddard, J.Davey, and G.Ladds (2006).
Investigating RGS proteins in yeast.
  Semin Cell Dev Biol, 17, 352-362.  
16460808 V.V.Gurevich, and E.V.Gurevich (2006).
The structural basis of arrestin-mediated regulation of G-protein-coupled receptors.
  Pharmacol Ther, 110, 465-502.  
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
15983037 L.L.Anderson, G.R.Marshall, E.Crocker, S.O.Smith, and T.J.Baranski (2005).
Motion of carboxyl terminus of Galpha is restricted upon G protein activation. A solution NMR study using semisynthetic Galpha subunits.
  J Biol Chem, 280, 31019-31026.  
16041481 N.G.Abdulaev, C.Zhang, A.Dinh, T.Ngo, P.N.Bryan, D.M.Brabazon, J.P.Marino, and K.D.Ridge (2005).
Bacterial expression and one-step purification of an isotope-labeled heterotrimeric G-protein alpha-subunit.
  J Biomol NMR, 32, 31-40.  
15898053 S.Albrizio, G.Caliendo, G.D'Errico, E.Novellino, P.Rovero, and A.M.D'Ursi (2005).
Galphas protein C-terminal alpha-helix at the interface: does the plasma membrane play a critical role in the Galphas protein functionality?
  J Pept Sci, 11, 617-626.  
16373322 W.R.Leifert, A.L.Aloia, O.Bucco, and E.J.McMurchie (2005).
GPCR-induced dissociation of G-protein subunits in early stage signal transduction.
  Mol Membr Biol, 22, 507-517.  
15128951 C.J.Thomas, X.Du, P.Li, Y.Wang, E.M.Ross, and S.R.Sprang (2004).
Uncoupling conformational change from GTP hydrolysis in a heterotrimeric G protein alpha-subunit.
  Proc Natl Acad Sci U S A, 101, 7560-7565.
PDB codes: 1svk 1svs
15189163 F.S.Willard, R.J.Kimple, and D.P.Siderovski (2004).
Return of the GDI: the GoLoco motif in cell division.
  Annu Rev Biochem, 73, 925-951.  
15595821 P.S.Park, S.Filipek, J.W.Wells, and K.Palczewski (2004).
Oligomerization of G protein-coupled receptors: past, present, and future.
  Biochemistry, 43, 15643-15656.  
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.  
14673086 M.Bünemann, M.Frank, and M.J.Lohse (2003).
Gi protein activation in intact cells involves subunit rearrangement rather than dissociation.
  Proc Natl Acad Sci U S A, 100, 16077-16082.  
12212810 A.M.Dursi, S.Albrizio, G.Greco, S.Mazzeo, M.R.Mazzoni, E.Novellino, and P.Rovero (2002).
Conformational analysis of the Galpha(s) protein C-terminal region.
  J Pept Sci, 8, 476-488.  
  12119276 L.S.Weinstein, M.Chen, and J.Liu (2002).
Gs(alpha) mutations and imprinting defects in human disease.
  Ann N Y Acad Sci, 968, 173-197.  
12146960 M.Medkova, A.M.Preininger, N.J.Yu, W.L.Hubbell, and H.E.Hamm (2002).
Conformational changes in the amino-terminal helix of the G protein alpha(i1) following dissociation from Gbetagamma subunit and activation.
  Biochemistry, 41, 9962-9972.  
11772024 M.Natochin, K.G.Gasimov, and N.O.Artemyev (2002).
A GPR-protein interaction surface of Gi(alpha): implications for the mechanism of GDP-release inhibition.
  Biochemistry, 41, 258-265.  
12455986 Q.Yang, S.I.Poole, and K.A.Borkovich (2002).
A G-protein beta subunit required for sexual and vegetative development and maintenance of normal G alpha protein levels in Neurospora crassa.
  Eukaryot Cell, 1, 378-390.  
10966476 E.M.Ross, and T.M.Wilkie (2000).
GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGS-like proteins.
  Annu Rev Biochem, 69, 795-827.  
10852703 F.J.Moy, P.K.Chanda, M.I.Cockett, W.Edris, P.G.Jones, K.Mason, S.Semus, and R.Powers (2000).
NMR structure of free RGS4 reveals an induced conformational change upon binding Galpha.
  Biochemistry, 39, 7063-7073.
PDB codes: 1ezt 1ezy
  11542857 J.A.Joseph, B.Shukitt-Hale, J.McEwen, B.M.Rabin, and B.M.Rabin (2000).
CNS-induced deficits of heavy particle irradiation in space: the aging connection.
  Adv Space Res, 25, 2057-2064.  
10747781 K.G.Muradov, and N.O.Artemyev (2000).
Coupling between the N- and C-terminal domains influences transducin-alpha intrinsic GDP/GTP exchange.
  Biochemistry, 39, 3937-3942.  
10639138 P.Lin, T.Fischer, T.Weiss, and M.G.Farquhar (2000).
Calnuc, an EF-hand Ca(2+) binding protein, specifically interacts with the C-terminal alpha5-helix of G(alpha)i3.
  Proc Natl Acad Sci U S A, 97, 674-679.  
10649434 V.Echeverría, M.V.Hinrichs, M.Torrejón, S.Ropero, J.Martinez, M.J.Toro, and J.Olate (2000).
Mutagenesis in the switch IV of the helical domain of the human Gsalpha reduces its GDP/GTP exchange rate.
  J Cell Biochem, 76, 368-375.  
10200251 D.R.Warner, and L.S.Weinstein (1999).
A mutation in the heterotrimeric stimulatory guanine nucleotide binding protein alpha-subunit with impaired receptor-mediated activation because of elevated GTPase activity.
  Proc Natl Acad Sci U S A, 96, 4268-4272.  
10371466 H.LeVine (1999).
Structural features of heterotrimeric G-protein-coupled receptors and their modulatory proteins.
  Mol Neurobiol, 19, 111-149.  
10403517 P.Chidiac, V.S.Markin, and E.M.Ross (1999).
Kinetic control of guanine nucleotide binding to soluble Galpha(q).
  Biochem Pharmacol, 58, 39-48.  
10518715 P.M.Jones, and A.M.George (1999).
Subunit interactions in ABC transporters: towards a functional architecture.
  FEMS Microbiol Lett, 179, 187-202.  
9637720 B.B.Lerman, B.Dong, K.M.Stein, S.M.Markowitz, J.Linden, and D.F.Catanzaro (1998).
Right ventricular outflow tract tachycardia due to a somatic cell mutation in G protein subunitalphai2.
  J Clin Invest, 101, 2862-2868.  
  9453500 C.D.Ulrich, M.Holtmann, and L.J.Miller (1998).
Secretin and vasoactive intestinal peptide receptors: members of a unique family of G protein-coupled receptors.
  Gastroenterology, 114, 382-397.  
9685182 C.Schauber, L.Chen, P.Tongaonkar, I.Vega, and K.Madura (1998).
Sequence elements that contribute to the degradation of yeast G alpha.
  Genes Cells, 3, 307-319.  
9727495 C.U.Lenzen, D.Steinmann, S.W.Whiteheart, and W.I.Weis (1998).
Crystal structure of the hexamerization domain of N-ethylmaleimide-sensitive fusion protein.
  Cell, 94, 525-536.
PDB code: 1d2n
9772163 D.E.Coleman, and S.R.Sprang (1998).
Crystal structures of the G protein Gi alpha 1 complexed with GDP and Mg2+: a crystallographic titration experiment.
  Biochemistry, 37, 14376-14385.
PDB code: 1bof
9485425 J.Scheuring, P.J.Berti, and V.L.Schramm (1998).
Transition-state structure for the ADP-ribosylation of recombinant Gialpha1 subunits by pertussis toxin.
  Biochemistry, 37, 2748-2758.  
  9753695 M.A.Wall, B.A.Posner, and S.R.Sprang (1998).
Structural basis of activity and subunit recognition in G protein heterotrimers.
  Structure, 6, 1169-1183.  
9461067 N.P.Skiba, and H.E.Hamm (1998).
How Gsalpha activates adenylyl cyclase.
  Nat Struct Biol, 5, 88-92.  
9539726 O.G.Kisselev, J.Kao, J.W.Ponder, Y.C.Fann, N.Gautam, and G.R.Marshall (1998).
Light-activated rhodopsin induces structural binding motif in G protein alpha subunit.
  Proc Natl Acad Sci U S A, 95, 4270-4275.
PDB code: 1aqg
9687499 S.Offermanns, L.P.Zhao, A.Gohla, I.Sarosi, M.I.Simon, and T.M.Wilkie (1998).
Embryonic cardiomyocyte hypoplasia and craniofacial defects in G alpha q/G alpha 11-mutant mice.
  EMBO J, 17, 4304-4312.  
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.  
9789008 W.Liu, and J.K.Northup (1998).
The helical domain of a G protein alpha subunit is a regulator of its effector.
  Proc Natl Acad Sci U S A, 95, 12878-12883.  
9675167 W.Wriggers, and K.Schulten (1998).
Nucleotide-dependent movements of the kinesin motor domain predicted by simulated annealing.
  Biophys J, 75, 646-661.  
  9265729 A.Bohm, R.Gaudet, and P.B.Sigler (1997).
Structural aspects of heterotrimeric G-protein signaling.
  Curr Opin Biotechnol, 8, 480-487.  
9305951 A.M.Gulick, C.B.Bauer, J.B.Thoden, and I.Rayment (1997).
X-ray structures of the MgADP, MgATPgammaS, and MgAMPPNP complexes of the Dictyostelium discoideum myosin motor domain.
  Biochemistry, 36, 11619-11628.
PDB codes: 1mma 1mmg 1mmn
9131251 D.E.Clapham, and E.J.Neer (1997).
G protein beta gamma subunits.
  Annu Rev Pharmacol Toxicol, 37, 167-203.  
9305638 G.R.Fanger, N.L.Johnson, and G.L.Johnson (1997).
MEK kinases are regulated by EGF and selectively interact with Rac/Cdc42.
  EMBO J, 16, 4961-4972.  
9204866 J.Scheuring, and V.L.Schramm (1997).
Pertussis toxin: transition state analysis for ADP-ribosylation of G-protein peptide alphai3C20.
  Biochemistry, 36, 8215-8223.  
9069252 M.R.Koelle (1997).
A new family of G-protein regulators - the RGS proteins.
  Curr Opin Cell Biol, 9, 143-147.  
9213227 R.E.Gundersen (1997).
Phosphorylation of the G protein alpha-subunit, G alpha 2, of Dictyostelium discoideum requires a functional and activated G alpha 2.
  J Cell Biochem, 66, 268-276.  
9242920 S.R.Sprang (1997).
G protein mechanisms: insights from structural analysis.
  Annu Rev Biochem, 66, 639-678.  
9434906 S.R.Sprang (1997).
G proteins, effectors and GAPs: structure and mechanism.
  Curr Opin Struct Biol, 7, 849-856.  
9056720 T.Gudermann, T.Schöneberg, and G.Schultz (1997).
Functional and structural complexity of signal transduction via G-protein-coupled receptors.
  Annu Rev Neurosci, 20, 399-427.  
9159128 T.Iiri, Z.Farfel, and H.R.Bourne (1997).
Conditional activation defect of a human Gsalpha mutant.
  Proc Natl Acad Sci U S A, 94, 5656-5661.  
9363787 T.Zor, M.Bar-Yaacov, S.Elgavish, B.Shaanan, and Z.Selinger (1997).
Rescue of a mutant G-protein by substrate-assisted catalysis.
  Eur J Biochem, 249, 330-336.  
  8939752 A.M.Berghuis, E.Lee, A.S.Raw, A.G.Gilman, and S.R.Sprang (1996).
Structure of the GDP-Pi complex of Gly203-->Ala gialpha1: a mimic of the ternary product complex of galpha-catalyzed GTP hydrolysis.
  Structure, 4, 1277-1290.
PDB code: 1git
  8740357 A.Wittinghofer (1996).
Deciphering the alphabet of G proteins: the structure of the alpha, beta, gamma heterotrimer.
  Structure, 4, 357-361.  
8785318 C.A.Smith, and I.Rayment (1996).
Active site comparisons highlight structural similarities between myosin and other P-loop proteins.
  Biophys J, 70, 1590-1602.  
8851656 D.E.Coleman, and S.R.Sprang (1996).
How G proteins work: a continuing story.
  Trends Biochem Sci, 21, 41-44.  
8791425 H.E.Hamm, and A.Gilchrist (1996).
Heterotrimeric G proteins.
  Curr Opin Cell Biol, 8, 189-196.  
8951093 H.Noji, T.Amano, and M.Yoshida (1996).
Molecular switch of F0F1-ATP synthase, G-protein, and other ATP-driven enzymes.
  J Bioenerg Biomembr, 28, 451-457.  
  8736548 I.Rayment (1996).
Kinesin and myosin: molecular motors with similar engines.
  Structure, 4, 501-504.  
8664266 M.J.Ryle, and L.C.Seefeldt (1996).
Elucidation of a MgATP signal transduction pathway in the nitrogenase iron protein: formation of a conformation resembling the MgATP-bound state by protein engineering.
  Biochemistry, 35, 4766-4775.  
9140202 M.Pellegrini, M.Royo, M.Chorev, and D.F.Mierke (1996).
Conformational characterization of a peptide mimetic of the third cytoplasmic loop of the G-protein coupled parathyroid hormone/parathyroid hormone related protein receptor.
  Biopolymers, 40, 653-666.  
8896589 R.D.Vale (1996).
Switches, latches, and amplifiers: common themes of G proteins and molecular motors.
  J Cell Biol, 135, 291-302.  
8521505 M.A.Wall, D.E.Coleman, E.Lee, J.A.Iñiguez-Lluhi, B.A.Posner, A.G.Gilman, and S.R.Sprang (1995).
The structure of the G protein heterotrimer Gi alpha 1 beta 1 gamma 2.
  Cell, 83, 1047-1058.
PDB codes: 1gg2 1gp2
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.