This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

6b8q

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 09:18, 18 December 2019

Crystal Structure of the Mg2+/CaM:Kv7.5 (KCNQ5) AB domain complex

Structural highlights

6b8q is a 8 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	KCNQ5 (HUMAN), CALM1, CALM, CAM, CAM1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[KCNQ5_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. [CALM1_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of CPVT4. The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of LQT14.

Function

[KCNQ5_HUMAN] Associates with KCNQ3 to form a potassium channel which contributes to M-type current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons. Therefore, it is important in the regulation of neuronal excitability. May contribute, with other potassium channels, to the molecular diversity of a heterogeneous population of M-channels, varying in kinetic and pharmacological properties, which underlie this physiologically important current. Insensitive to tetraethylammonium, but inhibited by barium, linopirdine and XE991. Activated by niflumic acid and the anticonvulsant retigabine. As the native M-channel, the potassium channel composed of KCNQ3 and KCNQ5 is also suppressed by activation of the muscarinic acetylcholine receptor CHRM1.^[1] ^[2] ^[3] [CALM1_HUMAN] Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696).^[4] ^[5] ^[6] ^[7]

Publication Abstract from PubMed

Kv7 (KCNQ) voltage-gated potassium channels control excitability in the brain, heart, and ear. Calmodulin (CaM) is crucial for Kv7 function, but how this calcium sensor affects activity has remained unclear. Here, we present X-ray crystallographic analysis of CaM:Kv7.4 and CaM:Kv7.5 AB domain complexes that reveal an Apo/CaM clamp conformation and calcium binding preferences. These structures, combined with small-angle X-ray scattering, biochemical, and functional studies, establish a regulatory mechanism for Kv7 CaM modulation based on a common architecture in which a CaM C-lobe calcium-dependent switch releases a shared Apo/CaM clamp conformation. This C-lobe switch inhibits voltage-dependent activation of Kv7.4 and Kv7.5 but facilitates Kv7.1, demonstrating that mechanism is shared by Kv7 isoforms despite the different directions of CaM modulation. Our findings provide a unified framework for understanding how CaM controls different Kv7 isoforms and highlight the role of membrane proximal domains for controlling voltage-gated channel function. VIDEO ABSTRACT.

A Calmodulin C-Lobe Ca(2+)-Dependent Switch Governs Kv7 Channel Function.,Chang A, Abderemane-Ali F, Hura GL, Rossen ND, Gate RE, Minor DL Jr. Neuron. 2018 Feb 21;97(4):836-852.e6. doi: 10.1016/j.neuron.2018.01.035. Epub, 2018 Feb 8. PMID:29429937^[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Lerche C, Scherer CR, Seebohm G, Derst C, Wei AD, Busch AE, Steinmeyer K. Molecular cloning and functional expression of KCNQ5, a potassium channel subunit that may contribute to neuronal M-current diversity. J Biol Chem. 2000 Jul 21;275(29):22395-400. doi: 10.1074/jbc.M002378200. PMID:10787416 doi:http://dx.doi.org/10.1074/jbc.M002378200
↑ Wickenden AD, Zou A, Wagoner PK, Jegla T. Characterization of KCNQ5/Q3 potassium channels expressed in mammalian cells. Br J Pharmacol. 2001 Jan;132(2):381-4. PMID:11159685 doi:http://dx.doi.org/10.1038/sj.bjp.0703861
↑ Lehman A, Thouta S, Mancini GMS, Naidu S, van Slegtenhorst M, McWalter K, Person R, Mwenifumbo J, Salvarinova R, Guella I, McKenzie MB, Datta A, Connolly MB, Kalkhoran SM, Poburko D, Friedman JM, Farrer MJ, Demos M, Desai S, Claydon T. Loss-of-Function and Gain-of-Function Mutations in KCNQ5 Cause Intellectual Disability or Epileptic Encephalopathy. Am J Hum Genet. 2017 Jul 6;101(1):65-74. doi: 10.1016/j.ajhg.2017.05.016. Epub, 2017 Jun 29. PMID:28669405 doi:http://dx.doi.org/10.1016/j.ajhg.2017.05.016
↑ Tsang WY, Spektor A, Luciano DJ, Indjeian VB, Chen Z, Salisbury JL, Sanchez I, Dynlacht BD. CP110 cooperates with two calcium-binding proteins to regulate cytokinesis and genome stability. Mol Biol Cell. 2006 Aug;17(8):3423-34. Epub 2006 Jun 7. PMID:16760425 doi:10.1091/mbc.E06-04-0371
↑ Reichow SL, Clemens DM, Freites JA, Nemeth-Cahalan KL, Heyden M, Tobias DJ, Hall JE, Gonen T. Allosteric mechanism of water-channel gating by Ca-calmodulin. Nat Struct Mol Biol. 2013 Jul 28. doi: 10.1038/nsmb.2630. PMID:23893133 doi:10.1038/nsmb.2630
↑ Boczek NJ, Gomez-Hurtado N, Ye D, Calvert ML, Tester DJ, Kryshtal D, Hwang HS, Johnson CN, Chazin WJ, Loporcaro CG, Shah M, Papez AL, Lau YR, Kanter R, Knollmann BC, Ackerman MJ. Spectrum and Prevalence of CALM1-, CALM2-, and CALM3-Encoded Calmodulin Variants in Long QT Syndrome and Functional Characterization of a Novel Long QT Syndrome-Associated Calmodulin Missense Variant, E141G. Circ Cardiovasc Genet. 2016 Apr;9(2):136-146. doi:, 10.1161/CIRCGENETICS.115.001323. Epub 2016 Mar 11. PMID:26969752 doi:http://dx.doi.org/10.1161/CIRCGENETICS.115.001323
↑ Yu CC, Ko JS, Ai T, Tsai WC, Chen Z, Rubart M, Vatta M, Everett TH 4th, George AL Jr, Chen PS. Arrhythmogenic calmodulin mutations impede activation of small-conductance calcium-activated potassium current. Heart Rhythm. 2016 Aug;13(8):1716-23. doi: 10.1016/j.hrthm.2016.05.009. Epub 2016, May 7. PMID:27165696 doi:http://dx.doi.org/10.1016/j.hrthm.2016.05.009
↑ Chang A, Abderemane-Ali F, Hura GL, Rossen ND, Gate RE, Minor DL Jr.. A Calmodulin C-Lobe Ca(2+)-Dependent Switch Governs Kv7 Channel Function. Neuron. 2018 Feb 21;97(4):836-852.e6. doi: 10.1016/j.neuron.2018.01.035. Epub, 2018 Feb 8. PMID:29429937 doi:http://dx.doi.org/10.1016/j.neuron.2018.01.035

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6b8q"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of the Mg2+/CaM:Kv7.5 (KCNQ5) AB domain complex==
-<StructureSection load='6b8q' size='340' side='right' caption='[[6b8q]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
+<StructureSection load='6b8q' size='340' side='right'caption='[[6b8q]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6b8q]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B8Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B8Q FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6b8q]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B8Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B8Q FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KCNQ5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CALM1, CALM, CAM, CAM1 ([http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6b8q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b8q OCA], [http://pdbe.org/6b8q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b8q RCSB], [http://www.ebi.ac.uk/pdbsum/6b8q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b8q ProSAT]</span></td></tr>
 </table>
@@ Line 20: / Line 21: @@
 </div>
 <div class="pdbe-citations 6b8q" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Calmodulin 3D structures|Calmodulin 3D structures]]
+*[[Potassium channel 3D structures|Potassium channel 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Abderemane-Ali, F]]
 [[Category: Chang, A]]

6b8q

From Proteopedia

Revision as of 09:18, 18 December 2019

Crystal Structure of the Mg2+/CaM:Kv7.5 (KCNQ5) AB domain complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox