PDBsum entry 1xod

Signaling protein

PDB id: 1xod

Contents

Protein chains

106 a.a. *

118 a.a. *

Ligands

GOL

Waters ×365

* Residue conservation analysis

PDB id:

1xod

Name:

Signaling protein

Title:

Crystal structure of x. Tropicalis spred1 evh-1 domain

Structure:

Spred1. Chain: a, b. Fragment: evh-1 domain. Engineered: yes

Source:

Xenopus tropicalis. Western clawed frog. Organism_taxid: 8364. Gene: spred1. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.15Å R-factor: 0.155 R-free: 0.177

Authors:

N.J.Harmer,J.M.Sivak,E.Amaya,T.L.Blundell

Key ref:

N.J.Harmer et al. (2005). 1.15 A crystal structure of the X. tropicalis Spred1 EVH1 domain suggests a fourth distinct peptide-binding mechanism within the EVH1 family. FEBS Lett, 579, 1161-1166. PubMed id: 15710406 DOI: 10.1016/j.febslet.2004.11.114

Date:

06-Oct-04 Release date: 25-Jan-05

Protein chain

Q66JG9  (SPRE1_XENTR) -  Sprouty-related, EVH1 domain-containing protein 1 from Xenopus tropicalis

Seq: 406 a.a.

Struc: 106 a.a.

Protein chain

Q66JG9  (SPRE1_XENTR) -  Sprouty-related, EVH1 domain-containing protein 1 from Xenopus tropicalis

Seq: 406 a.a.

Struc: 118 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1016/j.febslet.2004.11.114

FEBS Lett 579:1161-1166 (2005)

PubMed id: 15710406

1.15 A crystal structure of the X. tropicalis Spred1 EVH1 domain suggests a fourth distinct peptide-binding mechanism within the EVH1 family.

N.J.Harmer, J.M.Sivak, E.Amaya, T.L.Blundell.

ABSTRACT

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.

Selected figure(s)

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.

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.

The above figures are reprinted by permission from the Federation of European Biochemical Societies: FEBS Lett (2005, 579, 1161-1166) copyright 2005.

Figures were selected by an automated process.