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PDBsum entry 1fgy
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Signaling protein
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PDB id
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1fgy
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structural basis of 3-Phosphoinositide recognition by pleckstrin homology domains.
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Authors
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S.E.Lietzke,
S.Bose,
T.Cronin,
J.Klarlund,
A.Chawla,
M.P.Czech,
D.G.Lambright.
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Ref.
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Mol Cell, 2000,
6,
385-394.
[DOI no: ]
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PubMed id
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Abstract
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Lipid second messengers generated by phosphoinositide (PI) 3-kinases regulate
diverse cellular functions through interaction with pleckstrin homology (PH)
domains in modular signaling proteins. The PH domain of Grp1, a PI
3-kinase-activated exchange factor for Arf GTPases, selectively binds
phosphatidylinositol 3,4,5-trisphosphate with high affinity. We have determined
the structure of the Grp1 PH domain in the unliganded form and bound to inositol
1,3,4,5-tetraphosphate. A novel mode of phosphoinositide recognition involving a
20-residue insertion within the beta6/beta7 loop explains the unusually high
specificity of the Grp1 PH domain and the promiscuous 3-phosphoinositide binding
typical of several PH domains including that of protein kinase B. When compared
to other PH domains, general determinants of 3-phosphoinositide recognition and
specificity can be deduced.
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Figure 5.
Figure 5. Localized Structural Changes Accompanying Head
Group BindingOverlay of the unliganded (magenta) and
Ins(1,3,4,5)P[4]-bound (cyan) forms of the Grp1 PH domain
following superposition of Cα atoms.
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Figure 6.
Figure 6. Comparison of Ins(1,3,4,5)P[4] Recognition by the
Grp1 and Btk PH Domains(A) Space-filling representation with
invariant residues of the signature motif shown in white and
nonconserved residues from the three SDRs highlighted in green
(β1/β2 loop), magenta (β3/β4 loop), and orange (hairpin
insertion).(B) Schematic diagram showing direct interactions
with the head group. Residues in the signature motif are
indicated in blue.
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The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(2000,
6,
385-394)
copyright 2000.
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