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Gtp-binding protein
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PDB id
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1tad
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* Residue conservation analysis
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Gene Ontology (GO) functional annotation
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Cellular component
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photoreceptor inner segment
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6 terms
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Biological process
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response to stimulus
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18 terms
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Biochemical function
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acyl binding
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10 terms
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DOI no:
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Nature
372:276-279
(1994)
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PubMed id:
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GTPase mechanism of Gproteins from the 1.7-A crystal structure of transducin alpha-GDP-AIF-4.
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J.Sondek,
D.G.Lambright,
J.P.Noel,
H.E.Hamm,
P.B.Sigler.
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ABSTRACT
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Aluminium fluoride (AIF-4) activates members of the heterotrimeric G-protein (G
alpha beta gamma) family by binding to inactive G alpha.GDP near the site
occupied by the gamma-phosphate in G alpha.GTP (ref. 3). Here we describe the
crystal structure of transducin alpha.GDP activated with aluminium fluoride (Gt
alpha.GDP.AIF-4.H2O) at 1.7 A, a resolution sufficient to establish the
coordination geometry of the bound aluminium fluoride as well as the extensive
network of direct and water-mediated interactions that stabilize it. These
observations are derived from three independent representations in the
asymmetric unit, eliminating any chance of drawing conclusions based on
stereochemistry imposed by crystal packing. Surprisingly, aluminium fluoride
activates G alpha.GDP by binding with a geometry resembling a pentavalent
intermediate for GTP hydrolysis. The stabilizing interactions involve not only
residues that interact with the gamma-phosphate in Gt alpha.GTP gamma S, but
also conserved residues for GTPase activity. Thus the Gt alpha.GDP.AIF-4.H2O
structure provides new insight into the mechanism of GTP hydrolysis.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
|
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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.
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|
PDB code:
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B.Anand,
P.Surana,
and
B.Prakash
(2010).
Deciphering the catalytic machinery in 30S ribosome assembly GTPase YqeH.
|
| |
PLoS One, 5,
e9944.
|
|
|
|
|
|
|
J.V.Møller,
C.Olesen,
A.M.Winther,
and
P.Nissen
(2010).
The sarcoplasmic Ca2+-ATPase: design of a perfect chemi-osmotic pump.
|
| |
Q Rev Biophys, 43,
501-566.
|
|
|
|
|
|
|
L.Shen,
G.Caruso,
P.Bisegna,
D.Andreucci,
V.V.Gurevich,
H.E.Hamm,
and
E.Dibenedetto
(2010).
Dynamics of mouse rod phototransduction and its sensitivity to variation of key parameters.
|
| |
IET Syst Biol, 4,
12.
|
|
|
|
|
|
|
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:
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|
E.J.Heenan,
J.L.Vanhooke,
B.R.Temple,
L.Betts,
J.E.Sondek,
and
H.G.Dohlman
(2009).
Structure and function of Vps15 in the endosomal G protein signaling pathway.
|
| |
Biochemistry, 48,
6390-6401.
|
|
|
PDB code:
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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.
|
|
|
|
|
|
|
R.Gasper,
S.Meyer,
K.Gotthardt,
M.Sirajuddin,
and
A.Wittinghofer
(2009).
It takes two to tango: regulation of G proteins by dimerization.
|
| |
Nat Rev Mol Cell Biol, 10,
423-429.
|
|
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|
|
|
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T.Zielinski,
A.J.Kimple,
S.Q.Hutsell,
M.D.Koeff,
D.P.Siderovski,
and
R.G.Lowery
(2009).
Two Galpha(i1) rate-modifying mutations act in concert to allow receptor-independent, steady-state measurements of RGS protein activity.
|
| |
J Biomol Screen, 14,
1195-1206.
|
|
|
|
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|
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X.J.Yao,
G.Vélez Ruiz,
M.R.Whorton,
S.G.Rasmussen,
B.T.DeVree,
X.Deupi,
R.K.Sunahara,
and
B.Kobilka
(2009).
The effect of ligand efficacy on the formation and stability of a GPCR-G protein complex.
|
| |
Proc Natl Acad Sci U S A, 106,
9501-9506.
|
|
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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.
|
|
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|
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B.L.Grigorenko,
M.S.Shadrina,
I.A.Topol,
J.R.Collins,
and
A.V.Nemukhin
(2008).
Mechanism of the chemical step for the guanosine triphosphate (GTP) hydrolysis catalyzed by elongation factor Tu.
|
| |
Biochim Biophys Acta, 1784,
1908-1917.
|
|
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|
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B.T.Layden,
W.Saengsawang,
R.J.Donati,
S.Yang,
D.C.Mulhearn,
M.E.Johnson,
and
M.M.Rasenick
(2008).
Structural model of a complex between the heterotrimeric G protein, Gsalpha, and tubulin.
|
| |
Biochim Biophys Acta, 1783,
964-973.
|
|
|
|
|
|
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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.
|
|
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|
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|
|
K.C.Slep,
M.A.Kercher,
T.Wieland,
C.K.Chen,
M.I.Simon,
and
P.B.Sigler
(2008).
Molecular architecture of Galphao and the structural basis for RGS16-mediated deactivation.
|
| |
Proc Natl Acad Sci U S A, 105,
6243-6248.
|
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PDB codes:
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L.Gremer,
B.Gilsbach,
M.R.Ahmadian,
and
A.Wittinghofer
(2008).
Fluoride complexes of oncogenic Ras mutants to study the Ras-RasGap interaction.
|
| |
Biol Chem, 389,
1163-1171.
|
|
|
|
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|
|
S.A.Gabel,
and
R.E.London
(2008).
Ternary borate-nucleoside complex stabilization by ribonuclease A demonstrates phosphate mimicry.
|
| |
J Biol Inorg Chem, 13,
207-217.
|
|
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|
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|
|
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:
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B.Barren,
and
N.O.Artemyev
(2007).
Mechanisms of dominant negative G-protein alpha subunits.
|
| |
J Neurosci Res, 85,
3505-3514.
|
|
|
|
|
|
|
B.L.Grigorenko,
A.V.Nemukhin,
M.S.Shadrina,
I.A.Topol,
and
S.K.Burt
(2007).
Mechanisms of guanosine triphosphate hydrolysis by Ras and Ras-GAP proteins as rationalized by ab initio QM/MM simulations.
|
| |
Proteins, 66,
456-466.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
M.Bastepe
(2007).
The GNAS Locus: Quintessential Complex Gene Encoding Gsalpha, XLalphas, and other Imprinted Transcripts.
|
| |
Curr Genomics, 8,
398-414.
|
|
|
|
|
|
|
M.Jaffé,
and
J.Bubis
(2007).
Use of 5'-[p-(fluorosulfonyl)benzoyl] guanosine as an affinity probe for the guanine nucleotide-binding site of transducin.
|
| |
Protein J, 26,
125-133.
|
|
|
|
|
|
|
P.S.Crozier,
M.J.Stevens,
and
T.B.Woolf
(2007).
How a small change in retinal leads to G-protein activation: initial events suggested by molecular dynamics calculations.
|
| |
Proteins, 66,
559-574.
|
|
|
|
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|
|
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.
|
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PDB code:
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|
|
C.Galés,
J.J.Van Durm,
S.Schaak,
S.Pontier,
Y.Percherancier,
M.Audet,
H.Paris,
and
M.Bouvier
(2006).
Probing the activation-promoted structural rearrangements in preassembled receptor-G protein complexes.
|
| |
Nat Struct Mol Biol, 13,
778-786.
|
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|
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C.Hill,
A.Goddard,
J.Davey,
and
G.Ladds
(2006).
Investigating RGS proteins in yeast.
|
| |
Semin Cell Dev Biol, 17,
352-362.
|
|
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|
|
C.L.Piscitelli,
T.E.Angel,
B.W.Bailey,
P.Hargrave,
E.A.Dratz,
and
C.M.Lawrence
(2006).
Equilibrium between metarhodopsin-I and metarhodopsin-II is dependent on the conformation of the third cytoplasmic loop.
|
| |
J Biol Chem, 281,
6813-6825.
|
|
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PDB code:
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|
K.D.Ridge,
N.G.Abdulaev,
C.Zhang,
T.Ngo,
D.M.Brabazon,
and
J.P.Marino
(2006).
Conformational changes associated with receptor-stimulated guanine nucleotide exchange in a heterotrimeric G-protein alpha-subunit: NMR analysis of GTPgammaS-bound states.
|
| |
J Biol Chem, 281,
7635-7648.
|
|
|
|
|
|
|
L.S.Weinstein
(2006).
G(s)alpha mutations in fibrous dysplasia and McCune-Albright syndrome.
|
| |
J Bone Miner Res, 21,
P120-P124.
|
|
|
|
|
|
|
M.A.Anderson,
B.Ogbay,
O.G.Kisselev,
D.P.Cistola,
and
G.R.Marshall
(2006).
Alternate binding mode of C-terminal phenethylamine analogs of G(t)alpha(340-350) to photoactivated rhodopsin.
|
| |
Chem Biol Drug Des, 68,
295-307.
|
|
|
|
|
|
|
S.A.Chasse,
P.Flanary,
S.C.Parnell,
N.Hao,
J.Y.Cha,
D.P.Siderovski,
and
H.G.Dohlman
(2006).
Genome-scale analysis reveals Sst2 as the principal regulator of mating pheromone signaling in the yeast Saccharomyces cerevisiae.
|
| |
Eukaryot Cell, 5,
330-346.
|
|
|
|
|
|
|
S.Majumdar,
S.Ramachandran,
and
R.A.Cerione
(2006).
New insights into the role of conserved, essential residues in the GTP binding/GTP hydrolytic cycle of large G proteins.
|
| |
J Biol Chem, 281,
9219-9226.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
X.Pan,
S.Eathiraj,
M.Munson,
and
D.G.Lambright
(2006).
TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-finger mechanism.
|
| |
Nature, 442,
303-306.
|
|
|
PDB code:
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|
|
B.L.Grigorenko,
A.V.Nemukhin,
I.A.Topol,
R.E.Cachau,
and
S.K.Burt
(2005).
QM/MM modeling the Ras-GAP catalyzed hydrolysis of guanosine triphosphate.
|
| |
Proteins, 60,
495-503.
|
|
|
|
|
|
|
B.L.Grigorenko,
A.V.Nemukhin,
R.E.Cachau,
I.A.Topol,
and
S.K.Burt
(2005).
Computational study of a transition state analog of phosphoryl transfer in the Ras-RasGAP complex: AlF(x) versus MgF3-.
|
| |
J Mol Model, 11,
503-508.
|
|
|
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|
|
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.
|
|
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|
|
|
|
J.B.Thoden,
and
H.M.Holden
(2005).
The molecular architecture of human N-acetylgalactosamine kinase.
|
| |
J Biol Chem, 280,
32784-32791.
|
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PDB codes:
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|
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.
|
|
|
|
|
|
|
M.A.Schade,
N.K.Reynolds,
C.M.Dollins,
and
K.G.Miller
(2005).
Mutations that rescue the paralysis of Caenorhabditis elegans ric-8 (synembryn) mutants activate the G alpha(s) pathway and define a third major branch of the synaptic signaling network.
|
| |
Genetics, 169,
631-649.
|
|
|
|
|
|
|
M.E.Burns,
and
V.Y.Arshavsky
(2005).
Beyond counting photons: trials and trends in vertebrate visual transduction.
|
| |
Neuron, 48,
387-401.
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
N.G.Abdulaev,
T.Ngo,
C.Zhang,
A.Dinh,
D.M.Brabazon,
K.D.Ridge,
and
J.P.Marino
(2005).
Heterotrimeric G-protein alpha-subunit adopts a "preactivated" conformation when associated with betagamma-subunits.
|
| |
J Biol Chem, 280,
38071-38080.
|
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|
|
R.E.Burton,
T.A.Baker,
and
R.T.Sauer
(2005).
Nucleotide-dependent substrate recognition by the AAA+ HslUV protease.
|
| |
Nat Struct Mol Biol, 12,
245-251.
|
|
|
|
|
|
|
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.
|
|
|
|
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|
|
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:
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|
X.Gao,
Z.Du,
and
T.B.Patel
(2005).
Copper and zinc inhibit Galphas function: a nucleotide-free state of Galphas induced by Cu2+ and Zn2+.
|
| |
J Biol Chem, 280,
2579-2586.
|
|
|
|
|
|
|
Z.Chen,
W.D.Singer,
P.C.Sternweis,
and
S.R.Sprang
(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.
|
|
|
PDB code:
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|
B.C.Suh,
L.F.Horowitz,
W.Hirdes,
K.Mackie,
and
B.Hille
(2004).
Regulation of KCNQ2/KCNQ3 current by G protein cycling: the kinetics of receptor-mediated signaling by Gq.
|
| |
J Gen Physiol, 123,
663-683.
|
|
|
|
|
|
|
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:
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|
|
E.J.Helmreich
(2004).
Structural flexibility of small GTPases. Can it explain their functional versatility?
|
| |
Biol Chem, 385,
1121-1136.
|
|
|
|
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|
|
R.Herrmann,
M.Heck,
P.Henklein,
P.Henklein,
C.Kleuss,
K.P.Hofmann,
and
O.P.Ernst
(2004).
Sequence of interactions in receptor-G protein coupling.
|
| |
J Biol Chem, 279,
24283-24290.
|
|
|
|
|
|
|
S.Majumdar,
S.Ramachandran,
and
R.A.Cerione
(2004).
Perturbing the linker regions of the alpha-subunit of transducin: a new class of constitutively active GTP-binding proteins.
|
| |
J Biol Chem, 279,
40137-40145.
|
|
|
|
|
|
|
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:
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|
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.
|
|
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|
|
J.M.Manganello,
J.S.Huang,
T.Kozasa,
T.A.Voyno-Yasenetskaya,
and
G.C.Le Breton
(2003).
Protein kinase A-mediated phosphorylation of the Galpha13 switch I region alters the Galphabetagamma13-G protein-coupled receptor complex and inhibits Rho activation.
|
| |
J Biol Chem, 278,
124-130.
|
|
|
|
|
|
|
K.D.Ridge,
N.G.Abdulaev,
M.Sousa,
and
K.Palczewski
(2003).
Phototransduction: crystal clear.
|
| |
Trends Biochem Sci, 28,
479-487.
|
|
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|
|
|
M.Natochin,
and
N.O.Artemyev
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PDB codes:
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R.Vaiskunaite,
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Mol Cell, 6,
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PDB codes:
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C.T.Farrar,
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Structure, 8,
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PDB codes:
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M.Bähner,
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J Biol Chem, 275,
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Biochemistry, 39,
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J Biol Chem, 274,
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PDB code:
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Biochemistry, 38,
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Proteins, 36,
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Binding of the transition state analog MgADP-fluoroaluminate to F1-ATPase.
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J Biol Chem, 274,
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Biochemistry, 38,
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Visualization of the cysteinyl-phosphate intermediate of a protein-tyrosine phosphatase by x-ray crystallography.
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PDB code:
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A.E.Granovsky,
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Probing functional interfaces of rod PDE gamma-subunit using scanning fluorescent labeling.
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The importance of two conserved arginine residues for catalysis by the ras GTPase-activating protein, neurofibromin.
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Crystal structure of the hexamerization domain of N-ethylmaleimide-sensitive fusion protein.
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Cell, 94,
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PDB code:
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D.Barford,
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J Biol Chem, 273,
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Crystal structure of two quaternary complexes of dethiobiotin synthetase, enzyme-MgADP-AlF3-diaminopelargonic acid and enzyme-MgADP-dethiobiotin-phosphate; implications for catalysis.
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Protein Sci, 7,
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PDB codes:
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I.Rombel,
A.North,
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The bacterial enhancer-binding protein NtrC as a molecular machine.
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Cold Spring Harb Symp Quant Biol, 63,
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J.H.Wang,
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Raman difference studies of GDP and GTP binding to c-Harvey ras.
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Biochemistry, 37,
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Structure, 6,
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Near UV circular dichroism from biomimetic model compounds define the coordination geometry of vanadate centers in MeVi- and MeADPVi-rabbit myosin subfragment 1 complexes in solution.
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Biophys Chem, 71,
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Crystal structure of the thermosome, the archaeal chaperonin and homolog of CCT.
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Cell, 93,
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PDB codes:
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M.Jeschke,
G.J.Standke,
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Fluoroaluminate induces activation and association of Src and Pyk2 tyrosine kinases in osteoblastic MC3T3-E1 cells.
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Identification of effector residues on photoreceptor G protein, transducin.
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J Biol Chem, 273,
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PDB codes:
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N.P.Skiba,
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How Gsalpha activates adenylyl cyclase.
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Nat Struct Biol, 5,
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Proc Natl Acad Sci U S A, 95,
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PDB code:
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P.R.DiBello,
T.R.Garrison,
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How do the GTPases really work?
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Regulatory GTPases.
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T.P.Hopp
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Evidence from sequence information that the interleukin-1 receptor is a transmembrane GTPase.
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The most recent references are shown first.
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so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
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