title: 1.15 A crystal structure of the X. tropicalis Spred1 EVH1 domain suggests a fourth distinct peptide-binding mechanism within the EVH1 family.
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.
authors.affiliation: Department of Biochemistry, 80 Tennis Court Road, Cambridge, CB2 1GA, UK. nic@cryst.bioc.cam.ac.uk
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Harmer
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Sivak
authors.forename: Enrique
authors.initials: E
authors.lastname: Amaya
authors.forename: Tom L
authors.initials: TL
authors.lastname: Blundell
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D014981:Xenopus; D029867:Xenopus Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D029867:Xenopus Proteins