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PDBsum entry 1dro
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References listed in PDB file
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Key reference
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Title
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Solution structure of the pleckstrin homology domain of drosophila beta-Spectrin.
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Authors
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P.Zhang,
S.Talluri,
H.Deng,
D.Branton,
G.Wagner.
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Ref.
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Structure, 1995,
3,
1185-1195.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
perfect match.
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Abstract
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BACKGROUND: The pleckstrin homology (PH) domain, which is approximately 100
amino acids long, has been found in about 70 proteins involved in signal
transduction and cytoskeletal function, a frequency comparable to SH2 (src
homology 2) and SH3 domains. PH domains have been shown to bind the beta
gamma-subunits of G-proteins and phosphatidylinositol 4,5-bisphosphate (PIP2).
It is conceivable that the PH domain of beta-spectrin plays a part in the
association of spectrin with the plasma membrane of cells. RESULTS: We have
solved the solution structure of the 122-residue PH domain of Drosophila
beta-spectrin. The overall fold consists of two antiparallel beta-sheets packing
against each other at an angle of approximately 60 degrees to form a
beta-sandwich, a two-turn alpha-helix unique to spectrin PH domains, and a
four-turn C-terminal alpha-helix. One of the major insertions in beta-spectrin
PH domains forms a long, basic surface loop and appears to undergo slow
conformational exchange in solution. This loop shows big spectral changes upon
addition of D-myo-inositol 1,4,5-trisphosphate (IP3). CONCLUSIONS: We propose
that the groove at the outer surface of the second beta-sheet is an important
site of association with other proteins. This site and the possible
lipid-binding site can serve to localize the spectrin network under the plasma
membrane. More generally, it has to be considered that the common fold observed
for the PH domain structures solved so far does not necessarily mean that all PH
domains have similar functions. In fact, the residues constituting potential
binding sites for ligands or other proteins are only slightly conserved between
different PH domains.
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Figure 7.
Figure 7. A stereo view of the superposition of the 15 DspPH
structures. At the top is the groove formed by the outer surface
of the second β-sheet and the ill-defined β1/β2 loop and
β5/β6 loop. At the right, at the open edge of the β-sandwich
is the proposed PIP[2]-binding pocket. All backbone heavy atoms
are shown. Figure 7. A stereo view of the superposition of
the 15 DspPH structures. At the top is the groove formed by the
outer surface of the second β-sheet and the ill-defined β1/β2
loop and β5/β6 loop. At the right, at the open edge of the
β-sandwich is the proposed PIP[2]-binding pocket. All backbone
heavy atoms are shown.
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Figure 8.
Figure 8. Head-on view of the molecular surface of DspPH into
the groove on the outer surface of the second β-sheet, color
coded by electrostatic potential. The positive electrostatic
potential is shown in blue, the negative in red, and the neutral
in white. The β1/β2 loop is at the bottom, the β5/β6 loop
is at the top, and in between is the groove at the outer
surface of the second β-sheet. The figure was generated with
the program GRASP [42]. Figure 8. Head-on view of the
molecular surface of DspPH into the groove on the outer surface
of the second β-sheet, color coded by electrostatic potential.
The positive electrostatic potential is shown in blue, the
negative in red, and the neutral in white. The β1/β2 loop is
at the bottom, the β5/β6 loop is at the top, and in between is
the groove at the outer surface of the second β-sheet. The
figure was generated with the program GRASP [[3]42].
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The above figures are
reprinted
by permission from Cell Press:
Structure
(1995,
3,
1185-1195)
copyright 1995.
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