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[[Image:2ovc.gif|left|200px]]<br /><applet load="2ovc" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2ovc, resolution 2.070&Aring;" />
'''Crystal structure of a coiled-coil tetramerization domain from Kv7.4 channels'''<br />


==Overview==
==Crystal structure of a coiled-coil tetramerization domain from Kv7.4 channels==
Kv7.x (KCNQ) voltage-gated potassium channels form the cardiac and auditory I(Ks) current and the neuronal M-current. The five Kv7 subtypes have distinct assembly preferences encoded by a C-terminal cytoplasmic assembly domain, the A-domain Tail. Here, we present the high-resolution structure of the Kv7.4 A-domain Tail together with biochemical experiments that show that the domain is a self-assembling, parallel, four-stranded coiled coil. Structural analysis and biochemical studies indicate conservation of the coiled coil in all Kv7 subtypes and that a limited set of interactions encode assembly specificity determinants. Kv7 mutations have prominent roles in arrhythmias, deafness, and epilepsy. The structure together with biochemical data indicate that A-domain Tail arrhythmia mutations cluster on the solvent-accessible surface of the subunit interface at a likely site of action for modulatory proteins. Together, the data provide a framework for understanding Kv7 assembly specificity and the molecular basis of a distinct set of Kv7 channelopathies.
<StructureSection load='2ovc' size='340' side='right'caption='[[2ovc]], [[Resolution|resolution]] 2.07&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ovc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OVC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OVC FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.07&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ovc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ovc OCA], [https://pdbe.org/2ovc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ovc RCSB], [https://www.ebi.ac.uk/pdbsum/2ovc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ovc ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/KCNQ4_HUMAN KCNQ4_HUMAN] Defects in KCNQ4 are the cause of deafness autosomal dominant type 2A (DFNA2A) [MIM:[https://omim.org/entry/600101 600101]. DFNA2A is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.<ref>PMID:10025409</ref> <ref>PMID:10369879</ref> <ref>PMID:10571947</ref> <ref>PMID:10925378</ref> <ref>PMID:21242547</ref>
== Function ==
[https://www.uniprot.org/uniprot/KCNQ4_HUMAN KCNQ4_HUMAN] Probably important in the regulation of neuronal excitability. May underlie a potassium current involved in regulating the excitability of sensory cells of the cochlea. KCNQ4 channels are blocked by linopirdin, XE991 and bepridil, whereas clofilium is without significant effect. Muscarinic agonist oxotremorine-M strongly suppress KCNQ4 current in CHO cells in which cloned KCNQ4 channels were coexpressed with M1 muscarinic receptors.<ref>PMID:11245603</ref>


==Disease==
==See Also==
Known disease associated with this structure: Deafness, autosomal dominant 2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603537 603537]]
*[[Potassium channel 3D structures|Potassium channel 3D structures]]
 
== References ==
==About this Structure==
<references/>
2OVC is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OVC OCA].
__TOC__
 
</StructureSection>
==Reference==
Structural insight into KCNQ (Kv7) channel assembly and channelopathy., Howard RJ, Clark KA, Holton JM, Minor DL Jr, Neuron. 2007 Mar 1;53(5):663-75. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17329207 17329207]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Clark, K A.]]
[[Category: Clark KA]]
[[Category: Holton, J M.]]
[[Category: Holton JM]]
[[Category: Howard, R J.]]
[[Category: Howard RJ]]
[[Category: Minor, D L.]]
[[Category: Minor DL]]
[[Category: coiled-coil]]
[[Category: ion channel assembly]]
[[Category: potassium channel]]
[[Category: tetramer]]
[[Category: voltage-gated channel]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:22:57 2008''

Latest revision as of 12:06, 21 February 2024

Crystal structure of a coiled-coil tetramerization domain from Kv7.4 channelsCrystal structure of a coiled-coil tetramerization domain from Kv7.4 channels

Structural highlights

2ovc is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.07Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

KCNQ4_HUMAN Defects in KCNQ4 are the cause of deafness autosomal dominant type 2A (DFNA2A) [MIM:600101. DFNA2A is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.[1] [2] [3] [4] [5]

Function

KCNQ4_HUMAN Probably important in the regulation of neuronal excitability. May underlie a potassium current involved in regulating the excitability of sensory cells of the cochlea. KCNQ4 channels are blocked by linopirdin, XE991 and bepridil, whereas clofilium is without significant effect. Muscarinic agonist oxotremorine-M strongly suppress KCNQ4 current in CHO cells in which cloned KCNQ4 channels were coexpressed with M1 muscarinic receptors.[6]

See Also

References

  1. ↑ Kubisch C, Schroeder BC, Friedrich T, Lutjohann B, El-Amraoui A, Marlin S, Petit C, Jentsch TJ. KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness. Cell. 1999 Feb 5;96(3):437-46. PMID:10025409
  2. ↑ Coucke PJ, Van Hauwe P, Kelley PM, Kunst H, Schatteman I, Van Velzen D, Meyers J, Ensink RJ, Verstreken M, Declau F, Marres H, Kastury K, Bhasin S, McGuirt WT, Smith RJ, Cremers CW, Van de Heyning P, Willems PJ, Smith SD, Van Camp G. Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families. Hum Mol Genet. 1999 Jul;8(7):1321-8. PMID:10369879
  3. ↑ Talebizadeh Z, Kelley PM, Askew JW, Beisel KW, Smith SD. Novel mutation in the KCNQ4 gene in a large kindred with dominant progressive hearing loss. Hum Mutat. 1999;14(6):493-501. PMID:10571947 doi:<493::AID-HUMU8>3.0.CO;2-P 10.1002/(SICI)1098-1004(199912)14:6<493::AID-HUMU8>3.0.CO;2-P
  4. ↑ Van Hauwe P, Coucke PJ, Ensink RJ, Huygen P, Cremers CW, Van Camp G. Mutations in the KCNQ4 K+ channel gene, responsible for autosomal dominant hearing loss, cluster in the channel pore region. Am J Med Genet. 2000 Jul 31;93(3):184-7. PMID:10925378
  5. ↑ Arnett J, Emery SB, Kim TB, Boerst AK, Lee K, Leal SM, Lesperance MM. Autosomal dominant progressive sensorineural hearing loss due to a novel mutation in the KCNQ4 gene. Arch Otolaryngol Head Neck Surg. 2011 Jan;137(1):54-9. doi:, 10.1001/archoto.2010.234. PMID:21242547 doi:10.1001/archoto.2010.234
  6. ↑ Sogaard R, Ljungstrom T, Pedersen KA, Olesen SP, Jensen BS. KCNQ4 channels expressed in mammalian cells: functional characteristics and pharmacology. Am J Physiol Cell Physiol. 2001 Apr;280(4):C859-66. PMID:11245603

2ovc, resolution 2.07Å

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