2i0c
From Proteopedia
(New page: 200px<br /><applet load="2i0c" size="450" color="white" frame="true" align="right" spinBox="true" caption="2i0c, resolution 2.25Å" /> '''Crystal structure of...) |
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| - | [[Image:2i0c.gif|left|200px]]<br /><applet load="2i0c" size=" | + | [[Image:2i0c.gif|left|200px]]<br /><applet load="2i0c" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2i0c, resolution 2.25Å" /> | caption="2i0c, resolution 2.25Å" /> | ||
'''Crystal structure of the GluR6 ligand binding core dimer crosslinked by disulfide bonds between Y490C and L752C at 2.25 Angstroms Resolution'''<br /> | '''Crystal structure of the GluR6 ligand binding core dimer crosslinked by disulfide bonds between Y490C and L752C at 2.25 Angstroms Resolution'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Desensitization is a universal feature of ligand-gated ion channels. Using | + | Desensitization is a universal feature of ligand-gated ion channels. Using the crystal structure of the GluR2 L483Y mutant channel as a guide, we attempted to build non-desensitizing kainate-subtype glutamate receptors. Success was achieved for GluR5, GluR6 and GluR7 with intermolecular disulfide cross-links but not by engineering the dimer interface. Crystallographic analysis of the GluR6 Y490C L752C dimer revealed relaxation from the active conformation, which functional studies reveal is not sufficient to trigger desensitization. The equivalent non-desensitizing cross-linked GluR2 mutant retained weak sensitivity to a positive allosteric modulator, which had no effect on GluR2 L483Y. These results establish that the active conformation of AMPA and kainate receptors is conserved and further show that their desensitization requires dimer rearrangements, that subtle structural differences account for their diverse functional properties and that the ligand-binding core dimer is a powerful regulator of ion-channel activity. |
==About this Structure== | ==About this Structure== | ||
| - | 2I0C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with GLU as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 2I0C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=GLU:'>GLU</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I0C OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Mayer, M | + | [[Category: Mayer, M L.]] |
[[Category: GLU]] | [[Category: GLU]] | ||
[[Category: membrane protein]] | [[Category: membrane protein]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:47:41 2008'' |
Revision as of 15:47, 21 February 2008
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Crystal structure of the GluR6 ligand binding core dimer crosslinked by disulfide bonds between Y490C and L752C at 2.25 Angstroms Resolution
Overview
Desensitization is a universal feature of ligand-gated ion channels. Using the crystal structure of the GluR2 L483Y mutant channel as a guide, we attempted to build non-desensitizing kainate-subtype glutamate receptors. Success was achieved for GluR5, GluR6 and GluR7 with intermolecular disulfide cross-links but not by engineering the dimer interface. Crystallographic analysis of the GluR6 Y490C L752C dimer revealed relaxation from the active conformation, which functional studies reveal is not sufficient to trigger desensitization. The equivalent non-desensitizing cross-linked GluR2 mutant retained weak sensitivity to a positive allosteric modulator, which had no effect on GluR2 L483Y. These results establish that the active conformation of AMPA and kainate receptors is conserved and further show that their desensitization requires dimer rearrangements, that subtle structural differences account for their diverse functional properties and that the ligand-binding core dimer is a powerful regulator of ion-channel activity.
About this Structure
2I0C is a Single protein structure of sequence from Rattus norvegicus with as ligand. Full crystallographic information is available from OCA.
Reference
Conformational restriction blocks glutamate receptor desensitization., Weston MC, Schuck P, Ghosal A, Rosenmund C, Mayer ML, Nat Struct Mol Biol. 2006 Dec;13(12):1120-7. Epub 2006 Nov 19. PMID:17115050
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