1lbc: Difference between revisions
New page: left|200px<br /><applet load="1lbc" size="450" color="white" frame="true" align="right" spinBox="true" caption="1lbc, resolution 1.8Å" /> '''Crystal structure of ... |
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[[Image:1lbc.gif|left|200px]]<br /><applet load="1lbc" size=" | [[Image:1lbc.gif|left|200px]]<br /><applet load="1lbc" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1lbc, resolution 1.8Å" /> | caption="1lbc, resolution 1.8Å" /> | ||
'''Crystal structure of GluR2 ligand binding core (S1S2J-N775S) in complex with cyclothiazide (CTZ) as well as glutamate at 1.8 A resolution'''<br /> | '''Crystal structure of GluR2 ligand binding core (S1S2J-N775S) in complex with cyclothiazide (CTZ) as well as glutamate at 1.8 A resolution'''<br /> | ||
==Overview== | ==Overview== | ||
Ligand-gated ion channels transduce chemical signals into electrical | Ligand-gated ion channels transduce chemical signals into electrical impulses by opening a transmembrane pore in response to binding one or more neurotransmitter molecules. After activation, many ligand-gated ion channels enter a desensitized state in which the neurotransmitter remains bound but the ion channel is closed. Although receptor desensitization is crucial to the functioning of many ligand-gated ion channels in vivo, the molecular basis of this important process has until now defied analysis. Using the GluR2 AMPA-sensitive glutamate receptor, we show here that the ligand-binding cores form dimers and that stabilization of the intradimer interface by either mutations or allosteric modulators reduces desensitization. Perturbations that destabilize the interface enhance desensitization. Receptor activation involves conformational changes within each subunit that result in an increase in the separation of portions of the receptor that are linked to the ion channel. Our analysis defines the dimer interface in the resting and activated state, indicates how ligand binding is coupled to gating, and suggests modes of dimer dimer interaction in the assembled tetramer. Desensitization occurs through rearrangement of the dimer interface, which disengages the agonist-induced conformational change in the ligand-binding core from the ion channel gate. | ||
==About this Structure== | ==About this Structure== | ||
1LBC 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 ZN, GLU and CYZ as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 1LBC 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=ZN:'>ZN</scene>, <scene name='pdbligand=GLU:'>GLU</scene> and <scene name='pdbligand=CYZ:'>CYZ</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LBC OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: s1s2]] | [[Category: s1s2]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:43:20 2008'' | ||
Revision as of 14:43, 21 February 2008
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Crystal structure of GluR2 ligand binding core (S1S2J-N775S) in complex with cyclothiazide (CTZ) as well as glutamate at 1.8 A resolution
OverviewOverview
Ligand-gated ion channels transduce chemical signals into electrical impulses by opening a transmembrane pore in response to binding one or more neurotransmitter molecules. After activation, many ligand-gated ion channels enter a desensitized state in which the neurotransmitter remains bound but the ion channel is closed. Although receptor desensitization is crucial to the functioning of many ligand-gated ion channels in vivo, the molecular basis of this important process has until now defied analysis. Using the GluR2 AMPA-sensitive glutamate receptor, we show here that the ligand-binding cores form dimers and that stabilization of the intradimer interface by either mutations or allosteric modulators reduces desensitization. Perturbations that destabilize the interface enhance desensitization. Receptor activation involves conformational changes within each subunit that result in an increase in the separation of portions of the receptor that are linked to the ion channel. Our analysis defines the dimer interface in the resting and activated state, indicates how ligand binding is coupled to gating, and suggests modes of dimer dimer interaction in the assembled tetramer. Desensitization occurs through rearrangement of the dimer interface, which disengages the agonist-induced conformational change in the ligand-binding core from the ion channel gate.
About this StructureAbout this Structure
1LBC is a Single protein structure of sequence from Rattus norvegicus with , and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Mechanism of glutamate receptor desensitization., Sun Y, Olson R, Horning M, Armstrong N, Mayer M, Gouaux E, Nature. 2002 May 16;417(6886):245-53. PMID:12015593
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