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1t0j
From Proteopedia
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|PDB= 1t0j |SIZE=350|CAPTION= <scene name='initialview01'>1t0j</scene>, resolution 2.00Å | |PDB= 1t0j |SIZE=350|CAPTION= <scene name='initialview01'>1t0j</scene>, resolution 2.00Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=CL:CHLORIDE ION'>CL</scene> | + | |LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= CACNB2A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus]), CACNA1C, CACNL1A1, CCHL1A1, CACH2, CACN2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= CACNB2A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus]), CACNA1C, CACNL1A1, CCHL1A1, CACH2, CACN2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1toh|1TOH]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1t0j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t0j OCA], [http://www.ebi.ac.uk/pdbsum/1t0j PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1t0j RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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: Brugada syndrome 3 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=114205 114205]], Timothy syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=114205 114205]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Jr., D Minor.]] | [[Category: Jr., D Minor.]] | ||
[[Category: Petegem, F Van.]] | [[Category: Petegem, F Van.]] | ||
| - | [[Category: CL]] | ||
[[Category: aid]] | [[Category: aid]] | ||
[[Category: calcium channel]] | [[Category: calcium channel]] | ||
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[[Category: sh3 domain]] | [[Category: sh3 domain]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:49:30 2008'' |
Revision as of 20:49, 30 March 2008
| |||||||
| , resolution 2.00Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | CACNB2A (Rattus norvegicus), CACNA1C, CACNL1A1, CCHL1A1, CACH2, CACN2 (Homo sapiens) | ||||||
| Related: | 1TOH
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of a complex between voltage-gated calcium channel beta2a subunit and a peptide of the alpha1c subunit
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.
About this Structure
1T0J is a Protein complex structure of sequences from Homo sapiens and Rattus norvegicus. 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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