1t0j
From Proteopedia
(New page: 200px<br /> <applet load="1t0j" size="450" color="white" frame="true" align="right" spinBox="true" caption="1t0j, resolution 2.00Å" /> '''Crystal structure o...) |
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| - | [[Image:1t0j.gif|left|200px]]<br /> | + | [[Image:1t0j.gif|left|200px]]<br /><applet load="1t0j" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1t0j" size=" | + | |
caption="1t0j, resolution 2.00Å" /> | caption="1t0j, resolution 2.00Å" /> | ||
'''Crystal structure of a complex between voltage-gated calcium channel beta2a subunit and a peptide of the alpha1c subunit'''<br /> | '''Crystal structure of a complex between voltage-gated calcium channel beta2a subunit and a peptide of the alpha1c subunit'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Voltage-gated calcium channels (Ca(V)s) govern muscle contraction, hormone | + | Voltage-gated calcium channels (Ca(V)s) govern muscle contraction, hormone and neurotransmitter release, neuronal migration, activation of calcium-dependent signalling cascades, and synaptic input integration. An essential Ca(V) intracellular protein, the beta-subunit (Ca(V)beta), binds a conserved domain (the alpha-interaction domain, AID) between transmembrane domains I and II of the pore-forming alpha(1) subunit and profoundly affects multiple channel properties such as voltage-dependent activation, inactivation rates, G-protein modulation, drug sensitivity and cell surface expression. Here, we report the high-resolution crystal structures of the Ca(V)beta2a conserved core, alone and in complex with the AID. Previous work suggested that a conserved region, the beta-interaction domain (BID), formed the AID-binding site; however, this region is largely buried in the Ca(V)beta core and is unavailable for protein-protein interactions. The structure of the AID-Ca(V)beta2a complex shows instead that Ca(V)beta2a engages the AID through an extensive, conserved hydrophobic cleft (named the alpha-binding pocket, ABP). The ABP-AID interaction positions one end of the Ca(V)beta near the intracellular end of a pore-lining segment, called IS6, that has a critical role in Ca(V) inactivation. Together, these data suggest that Ca(V)betas influence Ca(V) gating by direct modulation of IS6 movement within the channel pore. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1T0J is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with CL as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1T0J is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=CL:'>CL</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T0J OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Chatelain, F.]] | [[Category: Chatelain, F.]] | ||
[[Category: Clark, K.]] | [[Category: Clark, K.]] | ||
| - | [[Category: Jr., D | + | [[Category: Jr., D Minor.]] |
| - | [[Category: Petegem, F | + | [[Category: Petegem, F Van.]] |
[[Category: CL]] | [[Category: CL]] | ||
[[Category: aid]] | [[Category: aid]] | ||
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[[Category: sh3 domain]] | [[Category: sh3 domain]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:08:35 2008'' |
Revision as of 13:08, 21 February 2008
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Crystal structure of a complex between voltage-gated calcium channel beta2a subunit and a peptide of the alpha1c subunit
Contents |
Overview
Voltage-gated calcium channels (Ca(V)s) govern muscle contraction, hormone and neurotransmitter release, neuronal migration, activation of calcium-dependent signalling cascades, and synaptic input integration. An essential Ca(V) intracellular protein, the beta-subunit (Ca(V)beta), binds a conserved domain (the alpha-interaction domain, AID) between transmembrane domains I and II of the pore-forming alpha(1) subunit and profoundly affects multiple channel properties such as voltage-dependent activation, inactivation rates, G-protein modulation, drug sensitivity and cell surface expression. Here, we report the high-resolution crystal structures of the Ca(V)beta2a conserved core, alone and in complex with the AID. Previous work suggested that a conserved region, the beta-interaction domain (BID), formed the AID-binding site; however, this region is largely buried in the Ca(V)beta core and is unavailable for protein-protein interactions. The structure of the AID-Ca(V)beta2a complex shows instead that Ca(V)beta2a engages the AID through an extensive, conserved hydrophobic cleft (named the alpha-binding pocket, ABP). The ABP-AID interaction positions one end of the Ca(V)beta near the intracellular end of a pore-lining segment, called IS6, that has a critical role in Ca(V) inactivation. Together, these data suggest that Ca(V)betas influence Ca(V) gating by direct modulation of IS6 movement within the channel pore.
Disease
Known diseases associated with this structure: Timothy syndrome OMIM:[114205]
About this Structure
1T0J is a Protein complex structure of sequences from Homo sapiens and Rattus norvegicus with as ligand. Full crystallographic information is available from OCA.
Reference
Structure of a complex between a voltage-gated calcium channel beta-subunit and an alpha-subunit domain., Van Petegem F, Clark KA, Chatelain FC, Minor DL Jr, Nature. 2004 Jun 10;429(6992):671-5. Epub 2004 May 12. PMID:15141227
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