6sz5

From Proteopedia

(Difference between revisions)

Current revision

Human calmodulin bound to a peptide of human NADPH oxidase 5

Structural highlights

6sz5 is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.23Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CALM2_HUMAN Catecholaminergic polymorphic ventricular tachycardia;Brugada syndrome;Romano-Ward syndrome. The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM2 are the cause of LQT15.

Function

CALM2_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).^[1] ^[2] ^[3]

Publication Abstract from PubMed

It is now accepted that Reactive Oxygen Species (ROS) are not only dangerous oxidative agents but also chemical mediators of the redox cell signaling and innate immune response. A central role in ROS controlled production is played by the NADPH oxidases (NOXs), a group of seven membrane-bound enzymes (NOX1-5 and DUOX1-2) whose unique function is to produce ROS. Here, we describe the regulation of NOX5, a widespread family-member present in cyanobacteria, protists, plants, fungi and the animal kingdom. We show that the calmodulin-like regulatory EF-domain of NOX5 is partially unfolded and detached from the rest of the protein in the absence of calcium. In the presence of calcium, the C-terminal lobe of the EF-domain acquires an ordered and more compact structure that enables its binding to the enzyme dehydrogenase domain. Our spectroscopic and mutagenesis studies further identified a set of conserved aspartate residues in the dehydrogenase domain that are essential for NOX5 activation. Altogether, our work shows that calcium induces an unfolded-to-folded transition of the EF-domain that promotes direct interaction with a conserved regulatory region, resulting in NOX5 activation.

On the mechanism of calcium-dependent activation of NADPH oxidase 5 (NOX5).,Millana-Fananas E, Todesca S, Siccorello A, Masino L, Pompach P, Magnani F, Pastore A, Mattevi A FEBS J. 2019 Nov 30. doi: 10.1111/febs.15160. PMID:31785178^[4]

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

References

↑ 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
↑ 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
↑ Millana-Fananas E, Todesca S, Siccorello A, Masino L, Pompach P, Magnani F, Pastore A, Mattevi A. On the mechanism of calcium-dependent activation of NADPH oxidase 5 (NOX5). FEBS J. 2019 Nov 30. doi: 10.1111/febs.15160. PMID:31785178 doi:http://dx.doi.org/10.1111/febs.15160

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/6sz5"

Categories: Homo sapiens | Large Structures | Mattevi A | Millana E

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6sz5 is ON HOLD
+==Human calmodulin bound to a peptide of human NADPH oxidase 5==
+<StructureSection load='6sz5' size='340' side='right'caption='[[6sz5]], [[Resolution|resolution]] 2.23&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6sz5]] is a 3 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=6SZ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SZ5 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.23&#8491;</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></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=6sz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sz5 OCA], [https://pdbe.org/6sz5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6sz5 RCSB], [https://www.ebi.ac.uk/pdbsum/6sz5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6sz5 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/CALM2_HUMAN CALM2_HUMAN] Catecholaminergic polymorphic ventricular tachycardia;Brugada syndrome;Romano-Ward syndrome. The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM2 are the cause of LQT15.
+== Function ==
+[https://www.uniprot.org/uniprot/CALM2_HUMAN CALM2_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).<ref>PMID:16760425</ref> <ref>PMID:26969752</ref> <ref>PMID:27165696</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+It is now accepted that Reactive Oxygen Species (ROS) are not only dangerous oxidative agents but also chemical mediators of the redox cell signaling and innate immune response. A central role in ROS controlled production is played by the NADPH oxidases (NOXs), a group of seven membrane-bound enzymes (NOX1-5 and DUOX1-2) whose unique function is to produce ROS. Here, we describe the regulation of NOX5, a widespread family-member present in cyanobacteria, protists, plants, fungi and the animal kingdom. We show that the calmodulin-like regulatory EF-domain of NOX5 is partially unfolded and detached from the rest of the protein in the absence of calcium. In the presence of calcium, the C-terminal lobe of the EF-domain acquires an ordered and more compact structure that enables its binding to the enzyme dehydrogenase domain. Our spectroscopic and mutagenesis studies further identified a set of conserved aspartate residues in the dehydrogenase domain that are essential for NOX5 activation. Altogether, our work shows that calcium induces an unfolded-to-folded transition of the EF-domain that promotes direct interaction with a conserved regulatory region, resulting in NOX5 activation.
-Authors: Millana, E., Mattevi, A.
+On the mechanism of calcium-dependent activation of NADPH oxidase 5 (NOX5).,Millana-Fananas E, Todesca S, Siccorello A, Masino L, Pompach P, Magnani F, Pastore A, Mattevi A FEBS J. 2019 Nov 30. doi: 10.1111/febs.15160. PMID:31785178<ref>PMID:31785178</ref>
-Description: Human calmodulin bound to a peptide of human NADPH oxidase 5
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Mattevi, A]]
+<div class="pdbe-citations 6sz5" style="background-color:#fffaf0;"></div>
-[[Category: Millana, E]]
+==See Also==
+*[[Calmodulin 3D structures|Calmodulin 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Mattevi A]]
+[[Category: Millana E]]

6sz5

From Proteopedia

Current revision

Human calmodulin bound to a peptide of human NADPH oxidase 5

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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