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PDBsum entry 1eaz
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Lipid binding protein
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PDB id
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1eaz
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Contents |
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* Residue conservation analysis
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Biochem J
358:287-294
(2001)
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PubMed id:
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Crystal structure of the phosphatidylinositol 3,4-bisphosphate-binding pleckstrin homology (PH) domain of tandem PH-domain-containing protein 1 (TAPP1): molecular basis of lipid specificity.
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C.C.Thomas,
S.Dowler,
M.Deak,
D.R.Alessi,
D.M.van Aalten.
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ABSTRACT
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Phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P(3)] and its immediate
breakdown product PtdIns(3,4)P(2) function as second messengers in growth
factor- and insulin-induced signalling pathways. One of the ways that these
3-phosphoinositides are known to regulate downstream signalling events is by
attracting proteins that possess specific PtdIns-binding pleckstrin homology
(PH) domains to the plasma membrane. Many of these proteins, such as protein
kinase B, phosphoinositide-dependent kinase 1 and the dual adaptor for
phosphotyrosine and 3-phosphoinositides (DAPP1) interact with both
PtdIns(3,4,5)P(3) and PtdIns(3,4)P(2) with similar affinity. Recently, a new
PH-domain-containing protein, termed tandem PH-domain-containing protein (TAPP)
1, was described which is the first protein reported to bind PtdIns(3,4)P(2)
specifically. Here we describe the crystal structure of the
PtdIns(3,4)P(2)-binding PH domain of TAPP1 at 1.4 A (1 A=0.1 nm) resolution in
complex with an ordered citrate molecule. The structure is similar to the known
structure of the PH domain of DAPP1 around the D-3 and D-4
inositol-phosphate-binding sites. However, a glycine residue adjacent to the D-5
inositol-phosphate-binding site in DAPP1 is substituted for a larger alanine
residue in TAPP1, which also induces a conformational change in the neighbouring
residues. We show that mutation of this glycine to alanine in DAPP1 converts
DAPP1 into a TAPP1-like PH domain that only interacts with PtdIns(3,4)P(2),
whereas the alanine to glycine mutation in TAPP1 permits the TAPP1 PH domain to
interact with PtdIns(3,4,5)P(3).
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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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S.Wullschleger,
D.H.Wasserman,
A.Gray,
K.Sakamoto,
and
D.R.Alessi
(2011).
Role of TAPP1 and TAPP2 adaptor binding to PtdIns(3,4)P2 in regulating insulin sensitivity defined by knock-in analysis.
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Biochem J,
434,
265-274.
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F.Campa,
H.Y.Yoon,
V.L.Ha,
Z.Szentpetery,
T.Balla,
and
P.A.Randazzo
(2009).
A PH domain in the Arf GTPase-activating protein (GAP) ARAP1 binds phosphatidylinositol 3,4,5-trisphosphate and regulates Arf GAP activity independently of recruitment to the plasma membranes.
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J Biol Chem,
284,
28069-28083.
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T.T.Zhang,
H.Li,
S.M.Cheung,
J.L.Costantini,
S.Hou,
M.Al-Alwan,
and
A.J.Marshall
(2009).
Phosphoinositide 3-kinase-regulated adapters in lymphocyte activation.
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Immunol Rev,
232,
255-272.
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W.S.Park,
W.D.Heo,
J.H.Whalen,
N.A.O'Rourke,
H.M.Bryan,
T.Meyer,
and
M.N.Teruel
(2008).
Comprehensive identification of PIP3-regulated PH domains from C. elegans to H. sapiens by model prediction and live imaging.
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Mol Cell,
30,
381-392.
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D.Manna,
A.Albanese,
W.S.Park,
and
W.Cho
(2007).
Mechanistic basis of differential cellular responses of phosphatidylinositol 3,4-bisphosphate- and phosphatidylinositol 3,4,5-trisphosphate-binding pleckstrin homology domains.
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J Biol Chem,
282,
32093-32105.
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P.Cohen
(2006).
The twentieth century struggle to decipher insulin signalling.
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Nat Rev Mol Cell Biol,
7,
867-873.
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S.G.Jackson,
Y.Zhang,
X.Bao,
K.Zhang,
R.Summerfield,
R.J.Haslam,
and
M.S.Junop
(2006).
Structure of the carboxy-terminal PH domain of pleckstrin at 2.1 Angstroms.
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Acta Crystallogr D Biol Crystallogr,
62,
324-330.
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PDB code:
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T.E.Rusten,
and
H.Stenmark
(2006).
Analyzing phosphoinositides and their interacting proteins.
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Nat Methods,
3,
251-258.
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C.C.Kumar,
and
V.Madison
(2005).
AKT crystal structure and AKT-specific inhibitors.
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Oncogene,
24,
7493-7501.
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C.Edlich,
G.Stier,
B.Simon,
M.Sattler,
and
C.Muhle-Goll
(2005).
Structure and phosphatidylinositol-(3,4)-bisphosphate binding of the C-terminal PH domain of human pleckstrin.
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Structure,
13,
277-286.
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PDB code:
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C.P.Downes,
A.Gray,
and
J.M.Lucocq
(2005).
Probing phosphoinositide functions in signaling and membrane trafficking.
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Trends Cell Biol,
15,
259-268.
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D.Delacour,
V.Gouyer,
J.P.Zanetta,
H.Drobecq,
E.Leteurtre,
G.Grard,
O.Moreau-Hannedouche,
E.Maes,
A.Pons,
S.André,
A.Le Bivic,
H.J.Gabius,
A.Manninen,
K.Simons,
and
G.Huet
(2005).
Galectin-4 and sulfatides in apical membrane trafficking in enterocyte-like cells.
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J Cell Biol,
169,
491-501.
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D.Komander,
A.Fairservice,
M.Deak,
G.S.Kular,
A.R.Prescott,
C.Peter Downes,
S.T.Safrany,
D.R.Alessi,
and
D.M.van Aalten
(2004).
Structural insights into the regulation of PDK1 by phosphoinositides and inositol phosphates.
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EMBO J,
23,
3918-3928.
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PDB codes:
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D.Komander,
M.Deak,
N.Morrice,
and
D.M.van Aalten
(2004).
Purification, crystallization and preliminary X-ray diffraction of a proteolytic fragment of PDK1 containing the pleckstrin homology domain.
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Acta Crystallogr D Biol Crystallogr,
60,
314-316.
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R.Irvine
(2004).
Inositol lipids: to PHix or not to PHix?
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Curr Biol,
14,
R308-R310.
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G.E.Cozier,
D.Bouyoucef,
and
P.J.Cullen
(2003).
Engineering the phosphoinositide-binding profile of a class I pleckstrin homology domain.
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J Biol Chem,
278,
39489-39496.
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M.A.Lemmon
(2003).
Phosphoinositide recognition domains.
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Traffic,
4,
201-213.
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P.Hilpelä,
P.Oberbanscheidt,
P.Hahne,
M.Hund,
G.Kalhammer,
J.V.Small,
and
M.Bähler
(2003).
SWAP-70 identifies a transitional subset of actin filaments in motile cells.
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Mol Biol Cell,
14,
3242-3253.
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S.M.Singh,
and
D.Murray
(2003).
Molecular modeling of the membrane targeting of phospholipase C pleckstrin homology domains.
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Protein Sci,
12,
1934-1953.
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A.Saxena,
P.Morozov,
D.Frank,
R.Musalo,
M.A.Lemmon,
E.Y.Skolnik,
and
B.Tycko
(2002).
Phosphoinositide binding by the pleckstrin homology domains of Ipl and Tih1.
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J Biol Chem,
277,
49935-49944.
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C.C.Thomas,
M.Deak,
D.R.Alessi,
and
D.M.van Aalten
(2002).
High-resolution structure of the pleckstrin homology domain of protein kinase b/akt bound to phosphatidylinositol (3,4,5)-trisphosphate.
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Curr Biol,
12,
1256-1262.
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PDB code:
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D.Karathanassis,
R.V.Stahelin,
J.Bravo,
O.Perisic,
C.M.Pacold,
W.Cho,
and
R.L.Williams
(2002).
Binding of the PX domain of p47(phox) to phosphatidylinositol 3,4-bisphosphate and phosphatidic acid is masked by an intramolecular interaction.
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EMBO J,
21,
5057-5068.
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PDB code:
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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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Links
