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{{STRUCTURE_4llo|  PDB=4llo  |  SCENE=  }}
===Structure of the eag domain-CNBHD complex of the mouse EAG1 channel===


==Function==
==Structure of the eag domain-CNBHD complex of the mouse EAG1 channel==
[[http://www.uniprot.org/uniprot/KCNH1_MOUSE KCNH1_MOUSE]] Pore-forming (alpha) subunit of voltage-gated non-inactivating delayed rectifier potassium channel. Channel properties may be modulated by cAMP and subunit assembly. Mediates IK(NI) current in myoblasts (By similarity).  
<StructureSection load='4llo' size='340' side='right'caption='[[4llo]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4llo]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LLO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LLO 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]] 1.995&#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=4llo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4llo OCA], [https://pdbe.org/4llo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4llo RCSB], [https://www.ebi.ac.uk/pdbsum/4llo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4llo ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/KCNH1_MOUSE KCNH1_MOUSE] Pore-forming (alpha) subunit of voltage-gated non-inactivating delayed rectifier potassium channel. Channel properties may be modulated by cAMP and subunit assembly. Mediates IK(NI) current in myoblasts (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The KCNH voltage-dependent potassium channels (ether-a-go-go, EAG; EAG-related gene, ERG; EAG-like channels, ELK) are important regulators of cellular excitability and have key roles in diseases such as cardiac long QT syndrome type 2 (LQT2), epilepsy, schizophrenia and cancer. The intracellular domains of KCNH channels are structurally distinct from other voltage-gated channels. The amino-terminal region contains an eag domain, which is composed of a Per-Arnt-Sim (PAS) domain and a PAS-cap domain, whereas the carboxy-terminal region contains a cyclic nucleotide-binding homology domain (CNBHD), which is connected to the pore through a C-linker domain. Many disease-causing mutations localize to these specialized intracellular domains, which underlie the unique gating and regulation of KCNH channels. It has been suggested that the eag domain may regulate the channel by interacting with either the S4-S5 linker or the CNBHD. Here we present a 2 A resolution crystal structure of the eag domain-CNBHD complex of the mouse EAG1 (also known as KCNH1) channel. It displays extensive interactions between the eag domain and the CNBHD, indicating that the regulatory mechanism of the eag domain primarily involves the CNBHD. Notably, the structure reveals that a number of LQT2 mutations at homologous positions in human ERG, in addition to cancer-associated mutations in EAG channels, localize to the eag domain-CNBHD interface. Furthermore, mutations at the interface produced marked effects on channel gating, demonstrating the important physiological role of the eag domain-CNBHD interaction. Our structure of the eag domain-CNBHD complex of mouse EAG1 provides unique insights into the physiological and pathophysiological mechanisms of KCNH channels.


==About this Structure==
The structural mechanism of KCNH-channel regulation by the eag domain.,Haitin Y, Carlson AE, Zagotta WN Nature. 2013 Sep 19;501(7467):444-8. doi: 10.1038/nature12487. Epub 2013 Aug 25. PMID:23975098<ref>PMID:23975098</ref>
[[4llo]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LLO OCA].
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4llo" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Potassium channel 3D structures|Potassium channel 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Carlson, A E.]]
[[Category: Carlson AE]]
[[Category: Haitin, Y.]]
[[Category: Haitin Y]]
[[Category: Zagotta, W N.]]
[[Category: Zagotta WN]]
[[Category: Transport protein]]
[[Category: Voltage-gated potassium channel]]

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