2ovc: Difference between revisions

New page: left|200px<br /> <applet load="2ovc" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ovc, resolution 2.070Å" /> '''Crystal structure ...
 
No edit summary
Line 1: Line 1:
[[Image:2ovc.gif|left|200px]]<br />
[[Image:2ovc.gif|left|200px]]<br /><applet load="2ovc" size="350" color="white" frame="true" align="right" spinBox="true"  
<applet load="2ovc" size="450" color="white" frame="true" align="right" spinBox="true"  
caption="2ovc, resolution 2.070&Aring;" />
caption="2ovc, resolution 2.070&Aring;" />
'''Crystal structure of a coiled-coil tetramerization domain from Kv7.4 channels'''<br />
'''Crystal structure of a coiled-coil tetramerization domain from Kv7.4 channels'''<br />


==Overview==
==Overview==
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.
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.


==Disease==
==Disease==
Line 11: Line 10:


==About this Structure==
==About this Structure==
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://ispc.weizmann.ac.il/oca-bin/ocashort?id=2OVC OCA].  
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].  


==Reference==
==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):663-675. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17329207 17329207]
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: Single protein]]
[[Category: Clark, K.A.]]
[[Category: Clark, K A.]]
[[Category: Holton, J.M.]]
[[Category: Holton, J M.]]
[[Category: Howard, R.J.]]
[[Category: Howard, R J.]]
[[Category: Minor, D.L.]]
[[Category: Minor, D L.]]
[[Category: coiled-coil]]
[[Category: coiled-coil]]
[[Category: ion channel assembly]]
[[Category: ion channel assembly]]
Line 27: Line 26:
[[Category: voltage-gated channel]]
[[Category: voltage-gated channel]]


''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 23:16:51 2007''
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:22:57 2008''

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA