7xni: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7xni]] is a 8 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=7XNI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XNI FirstGlance]. <br> | <table><tr><td colspan='2'>[[7xni]] is a 8 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=7XNI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XNI FirstGlance]. <br> | ||
</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=7xni FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xni OCA], [https://pdbe.org/7xni PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xni RCSB], [https://www.ebi.ac.uk/pdbsum/7xni PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xni ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.5Å</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=7xni FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xni OCA], [https://pdbe.org/7xni PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xni RCSB], [https://www.ebi.ac.uk/pdbsum/7xni PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xni ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Disease == | == Disease == | ||
| Line 10: | Line 11: | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/KCNQ1_HUMAN KCNQ1_HUMAN] Probably important in cardiac repolarization. Associates with KCNE1 (MinK) to form the I(Ks) cardiac potassium current. Elicits a rapidly activating, potassium-selective outward current. Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current in CHO cells in which cloned KCNQ1/KCNE1 channels were coexpressed with M1 muscarinic receptors. May associate also with KCNE3 (MiRP2) to form the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions, which is reduced in cystic fibrosis and pathologically stimulated in cholera and other forms of secretory diarrhea. | [https://www.uniprot.org/uniprot/KCNQ1_HUMAN KCNQ1_HUMAN] Probably important in cardiac repolarization. Associates with KCNE1 (MinK) to form the I(Ks) cardiac potassium current. Elicits a rapidly activating, potassium-selective outward current. Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current in CHO cells in which cloned KCNQ1/KCNE1 channels were coexpressed with M1 muscarinic receptors. May associate also with KCNE3 (MiRP2) to form the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions, which is reduced in cystic fibrosis and pathologically stimulated in cholera and other forms of secretory diarrhea. | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The cardiac KCNQ1 potassium channel carries the important I(Ks) current and controls the heart rhythm. Hundreds of mutations in KCNQ1 can cause life-threatening cardiac arrhythmia. Although KCNQ1 structures have been recently resolved, the structural basis for the dynamic electro-mechanical coupling, also known as the voltage sensor domain-pore domain (VSD-PD) coupling, remains largely unknown. In this study, utilizing two VSD-PD coupling enhancers, namely, the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP(2)) and a small-molecule ML277, we determined 2.5-3.5 A resolution cryo-electron microscopy structures of full-length human KCNQ1-calmodulin (CaM) complex in the apo closed, ML277-bound open, and ML277-PIP(2)-bound open states. ML277 binds at the "elbow" pocket above the S4-S5 linker and directly induces an upward movement of the S4-S5 linker and the opening of the activation gate without affecting the C-terminal domain (CTD) of KCNQ1. PIP(2) binds at the cleft between the VSD and the PD and brings a large structural rearrangement of the CTD together with the CaM to activate the PD. These findings not only elucidate the structural basis for the dynamic VSD-PD coupling process during KCNQ1 gating but also pave the way to develop new therapeutics for anti-arrhythmia. | |||
Structural mechanisms for the activation of human cardiac KCNQ1 channel by electro-mechanical coupling enhancers.,Ma D, Zhong L, Yan Z, Yao J, Zhang Y, Ye F, Huang Y, Lai D, Yang W, Hou P, Guo J Proc Natl Acad Sci U S A. 2022 Nov 8;119(45):e2207067119. doi: , 10.1073/pnas.2207067119. Epub 2022 Nov 3. PMID:36763058<ref>PMID:36763058</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7xni" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Potassium channel 3D structures|Potassium channel 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||