1vso
From Proteopedia
OCA (Talk | contribs)
(New page: 200px<br /><applet load="1vso" size="450" color="white" frame="true" align="right" spinBox="true" caption="1vso, resolution 1.85Å" /> '''Crystal Structure of...)
Next diff →
Revision as of 03:00, 21 November 2007
|
Crystal Structure of the Ligand-Binding Core of iGluR5 in Complex With the Antagonist (S)-ATPO at 1.85 A resolution
Overview
More than 50 structures have been reported on the ligand-binding core of, the ionotropic glutamate receptor iGluR2 that belongs to the AMPA-type of, receptors. In contrast, the ligand-binding core of the kainic acid-type, receptor iGluR5 has only been crystallized with three different ligands., Hence, additional structures of iGluR5 are needed to broaden the, understanding of the ligand-binding properties of iGluR5, and the, conformational changes leading to channel opening and closing. Here, we, present x-ray crystallographic data of two structures of the, ligand-binding core of iGluR5; one as a complex with the partial agonist, (2S,3S,4S)-3-carboxymethyl-4-[(1Z,3E,5R)-5-carboxy-1-methyl-hexa-1,3-dieny, l]-pyrrolidine-2-carboxylic acid (domoic acid) and one as a complex with, the antagonist, (S)-2-amino-3-[5-tert-butyl-3-(phosphonomethoxy)-4-isoxazolyl]propionic, acid [(S)-ATPO]. In agreement with the partial agonist activity of domoic, acid, the ligand-binding core of the iGluR5 complex is stabilized by, domoic acid in a conformation that is 11 degrees more open than the, conformation observed in the full agonist (S)-glutamic acid complex. This, is primarily caused by the 5-carboxy-1-methyl-hexa-1,3-dienyl moiety of, domoic acid and the residues Val685-Thr690 of iGluR5. In a more closed, conformation, these entities would lead to a steric clash. An even larger, domain opening of 28 degrees is introduced upon binding of the antagonist, (S)-ATPO. It appears that the span of domain opening is much larger in the, ligand-binding core of iGluR5 (30 degrees ) compared to what has been, observed in iGluR2 (19 degrees ). Similarly, much larger variation in the, distances between transmembrane linker residues in the two protomers, comprising the dimer is observed in iGluR5 as compared to iGluR2.
About this Structure
1VSO is a Single protein structure of sequence from Rattus norvegicus with AT1 and GOL as ligands. Full crystallographic information is available from OCA.
Reference
Partial agonism and antagonism of the ionotropic glutamate receptor iGLUR5: Structures of the ligand-binding core in complex with domoic acid and (S)-ATPO., Hald H, Naur P, Pickering DS, Sprogoe D, Madsen U, Timmermann DB, Ahring PK, Liljefors T, Schousboe A, Egebjerg J, Gajhede M, Kastrup JS, J Biol Chem. 2007 Jun 20;. PMID:17581823
Page seeded by OCA on Wed Nov 21 05:07:47 2007
