2be6
From Proteopedia
(New page: 200px<br /> <applet load="2be6" size="450" color="white" frame="true" align="right" spinBox="true" caption="2be6, resolution 2.000Å" /> '''2.0 A crystal stru...) |
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| - | [[Image:2be6.gif|left|200px]]<br /> | + | [[Image:2be6.gif|left|200px]]<br /><applet load="2be6" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="2be6, resolution 2.000Å" /> | caption="2be6, resolution 2.000Å" /> | ||
'''2.0 A crystal structure of the CaV1.2 IQ domain-Ca/CaM complex'''<br /> | '''2.0 A crystal structure of the CaV1.2 IQ domain-Ca/CaM complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Changes in activity-dependent calcium flux through voltage-gated calcium | + | Changes in activity-dependent calcium flux through voltage-gated calcium channels (Ca(V)s) drive two self-regulatory calcium-dependent feedback processes that require interaction between Ca(2+)/calmodulin (Ca(2+)/CaM) and a Ca(V) channel consensus isoleucine-glutamine (IQ) motif: calcium-dependent inactivation (CDI) and calcium-dependent facilitation (CDF). Here, we report the high-resolution structure of the Ca(2+)/CaM-Ca(V)1.2 IQ domain complex. The IQ domain engages hydrophobic pockets in the N-terminal and C-terminal Ca(2+)/CaM lobes through sets of conserved 'aromatic anchors.' Ca(2+)/N lobe adopts two conformations that suggest inherent conformational plasticity at the Ca(2+)/N lobe-IQ domain interface. Titration calorimetry experiments reveal competition between the lobes for IQ domain sites. Electrophysiological examination of Ca(2+)/N lobe aromatic anchors uncovers their role in Ca(V)1.2 CDF. Together, our data suggest that Ca(V) subtype differences in CDI and CDF are tuned by changes in IQ domain anchoring positions and establish a framework for understanding CaM lobe-specific regulation of Ca(V)s. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2BE6 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA and NI as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2BE6 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=NI:'>NI</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BE6 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Chatelain, F | + | [[Category: Chatelain, F C.]] |
| - | [[Category: Jr., D | + | [[Category: Jr., D L.Minor.]] |
| - | [[Category: Petegem, F | + | [[Category: Petegem, F Van.]] |
[[Category: CA]] | [[Category: CA]] | ||
[[Category: NI]] | [[Category: NI]] | ||
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[[Category: voltage-gated]] | [[Category: voltage-gated]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:36:53 2008'' |
Revision as of 14:36, 21 February 2008
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2.0 A crystal structure of the CaV1.2 IQ domain-Ca/CaM complex
Contents |
Overview
Changes in activity-dependent calcium flux through voltage-gated calcium channels (Ca(V)s) drive two self-regulatory calcium-dependent feedback processes that require interaction between Ca(2+)/calmodulin (Ca(2+)/CaM) and a Ca(V) channel consensus isoleucine-glutamine (IQ) motif: calcium-dependent inactivation (CDI) and calcium-dependent facilitation (CDF). Here, we report the high-resolution structure of the Ca(2+)/CaM-Ca(V)1.2 IQ domain complex. The IQ domain engages hydrophobic pockets in the N-terminal and C-terminal Ca(2+)/CaM lobes through sets of conserved 'aromatic anchors.' Ca(2+)/N lobe adopts two conformations that suggest inherent conformational plasticity at the Ca(2+)/N lobe-IQ domain interface. Titration calorimetry experiments reveal competition between the lobes for IQ domain sites. Electrophysiological examination of Ca(2+)/N lobe aromatic anchors uncovers their role in Ca(V)1.2 CDF. Together, our data suggest that Ca(V) subtype differences in CDI and CDF are tuned by changes in IQ domain anchoring positions and establish a framework for understanding CaM lobe-specific regulation of Ca(V)s.
Disease
Known diseases associated with this structure: Timothy syndrome OMIM:[114205]
About this Structure
2BE6 is a Protein complex structure of sequences from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
Insights into voltage-gated calcium channel regulation from the structure of the CaV1.2 IQ domain-Ca2+/calmodulin complex., Van Petegem F, Chatelain FC, Minor DL Jr, Nat Struct Mol Biol. 2005 Dec;12(12):1108-15. Epub 2005 Nov 20. PMID:16299511
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