6v5a: Difference between revisions
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==Crystal structure of the human BK channel gating ring L390P mutant== | ==Crystal structure of the human BK channel gating ring L390P mutant== | ||
<StructureSection load='6v5a' size='340' side='right'caption='[[6v5a]]' scene=''> | <StructureSection load='6v5a' size='340' side='right'caption='[[6v5a]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V5A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V5A FirstGlance]. <br> | <table><tr><td colspan='2'>[[6v5a]] is a 1 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=6V5A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V5A 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=6v5a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v5a OCA], [https://pdbe.org/6v5a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v5a RCSB], [https://www.ebi.ac.uk/pdbsum/6v5a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v5a ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=6v5a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v5a OCA], [https://pdbe.org/6v5a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v5a RCSB], [https://www.ebi.ac.uk/pdbsum/6v5a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v5a ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/KCMA1_HUMAN KCMA1_HUMAN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Large-conductance Ca(2+) and voltage-activated K(+) (BK) channels control membrane excitability in many cell types. BK channels are tetrameric. Each subunit is composed of a voltage sensor domain (VSD), a central pore-gate domain, and a large cytoplasmic domain (CTD) that contains the Ca(2+) sensors. While it is known that BK channels are activated by voltage and Ca(2+), and that voltage and Ca(2+) activations interact, less is known about the mechanisms involved. We explore here these mechanisms by examining the gating contribution of an interface formed between the VSDs and the alphaB helices located at the top of the CTDs. Proline mutations in the alphaB helix greatly decreased voltage activation while having negligible effects on gating currents. Analysis with the Horrigan, Cui, and Aldrich model indicated a decreased coupling between voltage sensors and pore gate. Proline mutations decreased Ca(2+) activation for both Ca(2+) bowl and RCK1 Ca(2+) sites, suggesting that both high-affinity Ca(2+) sites transduce their effect, at least in part, through the alphaB helix. Mg(2+) activation also decreased. The crystal structure of the CTD with proline mutation L390P showed a flattening of the first helical turn in the alphaB helix compared to wild type, without other notable differences in the CTD, indicating that structural changes from the mutation were confined to the alphaB helix. These findings indicate that an intact alphaB helix/VSD interface is required for effective coupling of Ca(2+) binding and voltage depolarization to pore opening and that shared Ca(2+) and voltage transduction pathways involving the alphaB helix may be involved. | |||
Coupling of Ca(2+) and voltage activation in BK channels through the alphaB helix/voltage sensor interface.,Geng Y, Deng Z, Zhang G, Budelli G, Butler A, Yuan P, Cui J, Salkoff L, Magleby KL Proc Natl Acad Sci U S A. 2020 Jun 23;117(25):14512-14521. doi:, 10.1073/pnas.1908183117. Epub 2020 Jun 8. PMID:32513714<ref>PMID:32513714</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6v5a" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Potassium channel 3D structures|Potassium channel 3D structures]] | *[[Potassium channel 3D structures|Potassium channel 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Deng Z]] | [[Category: Deng Z]] | ||
[[Category: Yuan P]] | [[Category: Yuan P]] | ||
Latest revision as of 11:03, 11 October 2023
Crystal structure of the human BK channel gating ring L390P mutantCrystal structure of the human BK channel gating ring L390P mutant
Structural highlights
FunctionPublication Abstract from PubMedLarge-conductance Ca(2+) and voltage-activated K(+) (BK) channels control membrane excitability in many cell types. BK channels are tetrameric. Each subunit is composed of a voltage sensor domain (VSD), a central pore-gate domain, and a large cytoplasmic domain (CTD) that contains the Ca(2+) sensors. While it is known that BK channels are activated by voltage and Ca(2+), and that voltage and Ca(2+) activations interact, less is known about the mechanisms involved. We explore here these mechanisms by examining the gating contribution of an interface formed between the VSDs and the alphaB helices located at the top of the CTDs. Proline mutations in the alphaB helix greatly decreased voltage activation while having negligible effects on gating currents. Analysis with the Horrigan, Cui, and Aldrich model indicated a decreased coupling between voltage sensors and pore gate. Proline mutations decreased Ca(2+) activation for both Ca(2+) bowl and RCK1 Ca(2+) sites, suggesting that both high-affinity Ca(2+) sites transduce their effect, at least in part, through the alphaB helix. Mg(2+) activation also decreased. The crystal structure of the CTD with proline mutation L390P showed a flattening of the first helical turn in the alphaB helix compared to wild type, without other notable differences in the CTD, indicating that structural changes from the mutation were confined to the alphaB helix. These findings indicate that an intact alphaB helix/VSD interface is required for effective coupling of Ca(2+) binding and voltage depolarization to pore opening and that shared Ca(2+) and voltage transduction pathways involving the alphaB helix may be involved. Coupling of Ca(2+) and voltage activation in BK channels through the alphaB helix/voltage sensor interface.,Geng Y, Deng Z, Zhang G, Budelli G, Butler A, Yuan P, Cui J, Salkoff L, Magleby KL Proc Natl Acad Sci U S A. 2020 Jun 23;117(25):14512-14521. doi:, 10.1073/pnas.1908183117. Epub 2020 Jun 8. PMID:32513714[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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