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PDBsum entry 1xod
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Signaling protein
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PDB id
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1xod
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References listed in PDB file
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Key reference
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Title
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1.15 a crystal structure of the X. Tropicalis spred1 evh1 domain suggests a fourth distinct peptide-Binding mechanism within the evh1 family.
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Authors
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N.J.Harmer,
J.M.Sivak,
E.Amaya,
T.L.Blundell.
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Ref.
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FEBS Lett, 2005,
579,
1161-1166.
[DOI no: ]
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PubMed id
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Abstract
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The recently described Spred protein family has been implicated in the
modulation of receptor tyrosine kinase signalling. We report the crystal
structure of the Enabled/vasodilator-stimulated phosphoprotein homology-1 (EVH1)
domain from Xenopus tropicalis Spred1, solved to 1.15 A resolution. This
structure confirms that the Spred EVH1 adopts the pleckstrin-homology fold, with
a similar secondary structure to Enabled. A translation of one of the
peptide-binding groove beta-strands narrows this groove, whilst one end of the
groove shows structural flexibility. We propose that Spred1 will bind peptides
that are less proline-rich than other EVH1 domains, with conformational changes
indicating an induced fit.
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Figure 1.
Fig. 1. Overview of X. tropicalis Spred1 EVH1 domain
structure. (a) Cartoon of secondary structure. Helices are shown
as rectangles, β-strands as arrows. Structure is shown with the
front sheet of the β-sandwich rotated about a hinge at the top
of the sandwich, represented by the dotted grey line. The front
sheet is shown in light grey, the back sheet in dark grey. The
β4–β5 loop is broken to rotate the top sheet, and is shown
by broken line. (b) Comparison of the two molecules observed in
the asymmetric unit. Structures are shown in the cartoon
representation. The lower view is rotated by 180° about the
vertical axis. Dark grey: molecule A; light grey: molecule B.
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Figure 4.
Fig. 4. Detail of key peptide binding residues (a)
Comparison of the positions of active site side chains. Strands
β1, β2 and β7 are shown for all molecules, with the remainder
of Spred1. W28 and F86 are shown as sticks. Backbone location of
selected residues is shown by white text. Colours: Spred1, red
(light red outside peptide-binding groove); Enabled, blue;
Homer, purple; WASP, black; nitrogen, blue (blue-grey: Spred1,
cyan: Enabled); oxygen, red. Spred W28, yellow arrowhead.
Homologous tryptophans, grey arrow. F86, black arrow. (b) The
Spred1 strand β2 is translated in comparison to the other EVH1
domains. Strands β1, β2 and β2′ are shown all molecules,
with the remainder of Spred1. Spred strand β2, black arrow;
Other EVH1 strand β2, dashed arrow. Colours as in (a). (c)
Comparison of Y21 equivalents in the two Spred1 structures. W28
and R/Y21 are shown as sticks. Colours as in (a), Spred1
molecule B in green. Enabled Y21, grey arrow. Spred1 R21 (two
conformations), black and yellow arrows.
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The above figures are
reprinted
by permission from the Federation of European Biochemical Societies:
FEBS Lett
(2005,
579,
1161-1166)
copyright 2005.
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