2l0w

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'''Unreleased structure'''
 
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The entry 2l0w is ON HOLD
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==Solution NMR structure of the N-terminal PAS domain of HERG potassium channel==
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<StructureSection load='2l0w' size='340' side='right'caption='[[2l0w]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2l0w]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L0W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L0W FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2l0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l0w OCA], [https://pdbe.org/2l0w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l0w RCSB], [https://www.ebi.ac.uk/pdbsum/2l0w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l0w ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/KCNH2_HUMAN KCNH2_HUMAN] Defects in KCNH2 are the cause of long QT syndrome type 2 (LQT2) [MIM:[https://omim.org/entry/613688 613688]. Long QT syndromes are heart disorders characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress. Deafness is often associated with LQT2.<ref>PMID:16361248</ref> <ref>PMID:9600240</ref> <ref>PMID:7889573</ref> <ref>PMID:8914737</ref> <ref>PMID:8635257</ref> <ref>PMID:8877771</ref> <ref>PMID:9024139</ref> <ref>PMID:9693036</ref> <ref>PMID:9544837</ref> <ref>PMID:9452080</ref> <ref>PMID:10086971</ref> <ref>PMID:10220144</ref> <ref>PMID:10187793</ref> <ref>PMID:10517660</ref> <ref>PMID:10735633</ref> <ref>PMID:10973849</ref> <ref>PMID:10862094</ref> <ref>PMID:10753933</ref> <ref>PMID:12062363</ref> <ref>PMID:12354768</ref> <ref>PMID:12621127</ref> <ref>PMID:15051636</ref> <ref>PMID:15840476</ref> <ref>PMID:22314138</ref> Defects in KCNH2 are the cause of short QT syndrome type 1 (SQT1) [MIM:[https://omim.org/entry/609620 609620]. Short QT syndromes are heart disorders characterized by idiopathic persistently and uniformly short QT interval on ECG in the absence of structural heart disease in affected individuals. They cause syncope and sudden death.<ref>PMID:14676148</ref> <ref>PMID:15828882</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/KCNH2_HUMAN KCNH2_HUMAN] Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoform 3 has no channel activity by itself, but modulates channel characteristics when associated with isoform 1.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The cytoplasmic N-terminal domain of the human ether-a-go-go related gene (hERG) K(+) channel is critical for the slow deactivation kinetics of the channel. However, the mechanism(s) by which the N-terminal domain regulates deactivation remains to be determined. Here we show that the solution NMR structure of the N-terminal 135 residues of hERG contains a previously described Per-Arnt-Sim (PAS) domain (residues 26-135) as well as an amphipathic alpha-helix (residues 13-23) and an initial unstructured segment (residues 2-9). Deletion of residues 2-25, only the unstructured segment (residues 2-9) or replacement of the alpha-helix with a flexible linker all result in enhanced rates of deactivation. Thus, both the initial flexible segment and the alpha-helix are required but neither is sufficient to confer slow deactivation kinetics. Alanine scanning mutagenesis identified R5 and G6 in the initial flexible segment as critical for slow deactivation. Alanine mutants in the helical region had less dramatic phenotypes. We propose that the PAS domain is bound close to the central core of the channel and that the N-terminal alpha-helix ensures that the flexible tail is correctly orientated for interaction with the activation gating machinery to stabilize the open state of the channel.
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Authors: Ng, C.A., Hunter, M., Mobli, M., King, G.F., Kuchel, P.W., Vandenberg, N.I.
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The N-Terminal Tail of hERG Contains an Amphipathic alpha-Helix That Regulates Channel Deactivation.,Ng CA, Hunter MJ, Perry MD, Mobli M, Ke Y, Kuchel PW, King GF, Stock D, Vandenberg JI PLoS One. 2011 Jan 13;6(1):e16191. PMID:21249148<ref>PMID:21249148</ref>
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Description: Solution NMR structure of the N-terminal PAS domain of HERG potassium channel
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Aug 18 11:15:11 2010''
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<div class="pdbe-citations 2l0w" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Hunter MJ]]
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[[Category: King GF]]
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[[Category: Kuchel PW]]
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[[Category: Mobli M]]
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[[Category: Ng CA]]
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[[Category: Vandenberg JI]]

Current revision

Solution NMR structure of the N-terminal PAS domain of HERG potassium channel

PDB ID 2l0w

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