2l1m: Difference between revisions

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 ==Solution structure of the eag domain of the hERG (Kv11.1) K+ channel==
-<StructureSection load='2l1m' size='340' side='right'caption='[[2l1m]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='2l1m' size='340' side='right'caption='[[2l1m]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2l1m]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L1M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L1M FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2l1m]] 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=2L1M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L1M FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1byw|1byw]]</div></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KCNH2, ERG, ERG1, HERG ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2l1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l1m OCA], [https://pdbe.org/2l1m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l1m RCSB], [https://www.ebi.ac.uk/pdbsum/2l1m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l1m ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[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>
+[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>
 == Function ==
-[[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.
+[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.
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-Human ether-a-go-go related gene (hERG) K+ channels have a critical role in cardiac repolarisation. hERG channels close (deactivate) very slowly and this is vital for regulating the time-course and amplitude of repolarising current during the cardiac action potential. Accelerated deactivation is one mechanism by which inherited mutations cause long QT syndrome and potentially lethal arrhythmias. hERG deactivation is highly dependent upon an intact eag domain (the first 135 amino acids of the N-terminus). Importantly, deletion of residues 2-26 accelerates deactivation to a similar extent as removing the entire eag domain. These and other experiments suggest the first 26 residues (NT1-26) contain structural elements required to slow deactivation by stabilising the open conformation of the pore. Residues 26-135 form a PAS domain, but a structure for NT1-26 has not been forthcoming and little is known about its site of interaction on the channel. In this study, we present an NMR structure for the entire eag domain, which reveals that NT1-26 is structurally independent from the PAS domain and contains a stable amphipathic helix with one face being positively charged. Mutagenesis and electrophysiological studies indicate that neutralising basic residues and breaking the amphipathic helix dramatically accelerate deactivation. Furthermore, scanning mutagenesis and molecular modelling studies of the cyclic nucleotide binding domain (cNBD) suggest that negatively charged patches on its cytoplasmic surface form an interface with the NT1-26 domain. We propose a model in which NT1-26 obstructs gating motions of the cNBD to allosterically stabilise the open conformation of the pore.
-Mechanistic insight into hERG K+ channel deactivation gating from the solution structure of the EAG domain.,Muskett FW, Thouta S, Thomson SJ, Bowen A, Stansfeld PJ, Mitcheson JS J Biol Chem. 2010 Dec 6. PMID:21135103<ref>PMID:21135103</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 2l1m" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 28: / Line 18: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Mitcheson, J S]]
+[[Category: Mitcheson JS]]
-[[Category: Muskett, F W]]
+[[Category: Muskett FW]]
-[[Category: Eag domain]]
-[[Category: Herg]]
-[[Category: Kv11 1]]
-[[Category: Pas domain]]
-[[Category: Transport protein]]