3bj4
From Proteopedia
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|PDB= 3bj4 |SIZE=350|CAPTION= <scene name='initialview01'>3bj4</scene>, resolution 2.00Å | |PDB= 3bj4 |SIZE=350|CAPTION= <scene name='initialview01'>3bj4</scene>, resolution 2.00Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=NI:NICKEL (II) ION'>NI</scene> | + | |LIGAND= <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= KCNQ1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= KCNQ1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bj4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bj4 OCA], [http://www.ebi.ac.uk/pdbsum/3bj4 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=3bj4 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
The Kv7 subfamily of voltage-dependent potassium channels, distinct from other subfamilies by dint of its large intracellular C-terminus, acts to regulate excitability in cardiac and neuronal tissues. KCNQ1 (Kv7.1), the founding subfamily member, encodes a channel subunit directly implicated in genetic disorders such as the long QT (LQT) syndrome, a cardiac pathology responsible for arrhythmias. We have used a recombinant protein preparation of the C-terminus to probe the structure and function of this domain and its individual modules. The C-terminus proximal half associates with one calmodulin (CaM) constitutively bound to each subunit where CaM is critical for proper folding of the whole intracellular domain. The distal half directs tetramerization, employing tandem coiled-coils. The first coiled-coil complex is dimeric that undergoes concentration-dependent self-association to form a dimer of dimers. The outer coiled-coil is parallel tetrameric, whose details have been elucidated based on 2.0 A crystallographic data. Both coiled-coils act in a coordinate fashion to mediate the formation and stabilization of the tetrameric distal half. Functional studies including characterization of structure-based and LQT mutants prove the requirement for both modules and point to complex roles for these modules including folding, assembly, trafficking and regulation. | The Kv7 subfamily of voltage-dependent potassium channels, distinct from other subfamilies by dint of its large intracellular C-terminus, acts to regulate excitability in cardiac and neuronal tissues. KCNQ1 (Kv7.1), the founding subfamily member, encodes a channel subunit directly implicated in genetic disorders such as the long QT (LQT) syndrome, a cardiac pathology responsible for arrhythmias. We have used a recombinant protein preparation of the C-terminus to probe the structure and function of this domain and its individual modules. The C-terminus proximal half associates with one calmodulin (CaM) constitutively bound to each subunit where CaM is critical for proper folding of the whole intracellular domain. The distal half directs tetramerization, employing tandem coiled-coils. The first coiled-coil complex is dimeric that undergoes concentration-dependent self-association to form a dimer of dimers. The outer coiled-coil is parallel tetrameric, whose details have been elucidated based on 2.0 A crystallographic data. Both coiled-coils act in a coordinate fashion to mediate the formation and stabilization of the tetrameric distal half. Functional studies including characterization of structure-based and LQT mutants prove the requirement for both modules and point to complex roles for these modules including folding, assembly, trafficking and regulation. | ||
| + | |||
| + | ==Disease== | ||
| + | Known disease associated with this structure: Atrial fibrillation, familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607542 607542]], Jervell and Lange-Nielsen syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607542 607542]], Long QT syndrome-1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607542 607542]], Short QT syndrome-2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607542 607542]], Torsades de pointes, drug-associated OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607542 607542]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Hirsch, J A.]] | [[Category: Hirsch, J A.]] | ||
[[Category: Wiener, R.]] | [[Category: Wiener, R.]] | ||
| - | [[Category: NI]] | ||
[[Category: alternative splicing]] | [[Category: alternative splicing]] | ||
[[Category: coiled coil]] | [[Category: coiled coil]] | ||
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[[Category: voltage-gated channel]] | [[Category: voltage-gated channel]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:26:49 2008'' |
Revision as of 02:26, 31 March 2008
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| , resolution 2.00Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | KCNQ1 (Homo sapiens) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
The KCNQ1 (Kv7.1) C-terminus, a multi-tiered scaffold for subunit assembly and protein interaction
Contents |
Overview
The Kv7 subfamily of voltage-dependent potassium channels, distinct from other subfamilies by dint of its large intracellular C-terminus, acts to regulate excitability in cardiac and neuronal tissues. KCNQ1 (Kv7.1), the founding subfamily member, encodes a channel subunit directly implicated in genetic disorders such as the long QT (LQT) syndrome, a cardiac pathology responsible for arrhythmias. We have used a recombinant protein preparation of the C-terminus to probe the structure and function of this domain and its individual modules. The C-terminus proximal half associates with one calmodulin (CaM) constitutively bound to each subunit where CaM is critical for proper folding of the whole intracellular domain. The distal half directs tetramerization, employing tandem coiled-coils. The first coiled-coil complex is dimeric that undergoes concentration-dependent self-association to form a dimer of dimers. The outer coiled-coil is parallel tetrameric, whose details have been elucidated based on 2.0 A crystallographic data. Both coiled-coils act in a coordinate fashion to mediate the formation and stabilization of the tetrameric distal half. Functional studies including characterization of structure-based and LQT mutants prove the requirement for both modules and point to complex roles for these modules including folding, assembly, trafficking and regulation.
Disease
Known disease associated with this structure: Atrial fibrillation, familial OMIM:[607542], Jervell and Lange-Nielsen syndrome OMIM:[607542], Long QT syndrome-1 OMIM:[607542], Short QT syndrome-2 OMIM:[607542], Torsades de pointes, drug-associated OMIM:[607542]
About this Structure
3BJ4 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The KCNQ1 (Kv7.1) C-terminus, a multi-tieredscaffold for subunit assembly and protein interaction., Wiener R, Haitin Y, Shamgar L, Fernandez-Alonso MC, Martos A, Chomsky-Hecht O, Rivas G, Attali B, Hirsch JA, J Biol Chem. 2007 Dec 29;. PMID:18165683
Page seeded by OCA on Mon Mar 31 05:26:49 2008
Categories: Homo sapiens | Single protein | Hirsch, J A. | Wiener, R. | Alternative splicing | Coiled coil | Deafness | Disease mutation | Glycoprotein | Ion transport | Ionic channel | Long qt syndrome | Membrane | Phosphoprotein | Polymorphism | Potassium | Potassium channel | Potassium transport | Short qt syndrome | Signaling protein | Transmembrane | Transport | Voltage-gated channel
