5oeo

From Proteopedia

(Difference between revisions)

Current revision

Solution structure of the complex of TRPV5(655-725) with a Calmodulin E32Q/E68Q double mutant

Structural highlights

5oeo is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

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

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).^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

The transient receptor potential vanilloid channel subfamily member 5 (TRPV5) is a highly selective calcium ion channel predominately expressed in the kidney epithelium that plays an essential role in calcium reabsorption from renal infiltrate. In order to maintain Ca(2+) homeostasis, TRPV5 possesses a tightly regulated negative feedback mechanism, where the ubiquitous Ca(2+) binding protein calmodulin (CaM) directly binds to the intracellular TRPV5 C-terminus, thus regulating TRPV5. Here we report on the characterization of the TRPV5 C-terminal CaM binding site and its interaction with CaM at an atomistic level. We have solved the de novo solution structure of the TRPV5 C-terminus in complex with a CaM mutant, creating conditions that mimic the cellular basal Ca(2+) state. We demonstrate that under these conditions the TRPV5 C-terminus is exclusively bound to the CaM C-lobe only, while it confers conformational freedom to the CaM N-lobe. We also show that at elevated calcium levels, additional interactions between the TRPV5 C-terminus and CaM N-lobe occur, resulting in formation of a tight 1:1 complex, effectively making the N-lobe the calcium sensor. Together, these data are consistent with and support the novel model for Ca(2+)/CaM-dependent inactivation of TRPV channels as proposed by Bate and co-workers [ Bate , N. , et al. ( 2018 ) Biochemistry , ( 57), DOI: 10.1021/acs.biochem.7b01286 ].

The Structural Basis of Calcium-Dependent Inactivation of the Transient Receptor Potential Vanilloid 5 Channel.,Bokhovchuk FM, Bate N, Kovalevskaya NV, Goult BT, Spronk CAEM, Vuister GW Biochemistry. 2018 Apr 20. doi: 10.1021/acs.biochem.7b01287. PMID:29584409^[5]

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
↑ 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
↑ Bokhovchuk FM, Bate N, Kovalevskaya NV, Goult BT, Spronk CAEM, Vuister GW. The Structural Basis of Calcium-Dependent Inactivation of the Transient Receptor Potential Vanilloid 5 Channel. Biochemistry. 2018 Apr 20. doi: 10.1021/acs.biochem.7b01287. PMID:29584409 doi:http://dx.doi.org/10.1021/acs.biochem.7b01287

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/5oeo"

@@ Line 1: / Line 1: @@
 ==Solution structure of the complex of TRPV5(655-725) with a Calmodulin E32Q/E68Q double mutant==
-<StructureSection load='5oeo' size='340' side='right' caption='[[5oeo]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='5oeo' size='340' side='right'caption='[[5oeo]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5oeo]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OEO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OEO FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5oeo]] is a 2 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=5OEO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OEO FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></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='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=5oeo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oeo OCA], [http://pdbe.org/5oeo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5oeo RCSB], [http://www.ebi.ac.uk/pdbsum/5oeo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5oeo ProSAT]</span></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=5oeo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oeo OCA], [https://pdbe.org/5oeo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5oeo RCSB], [https://www.ebi.ac.uk/pdbsum/5oeo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5oeo ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/CALM1_HUMAN 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.
+[https://www.uniprot.org/uniprot/CALM1_HUMAN 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 ==
-[[http://www.uniprot.org/uniprot/CALM1_HUMAN 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).<ref>PMID:16760425</ref> <ref>PMID:23893133</ref> <ref>PMID:26969752</ref> <ref>PMID:27165696</ref>  [[http://www.uniprot.org/uniprot/TRPV5_HUMAN TRPV5_HUMAN]] Constitutively active calcium selective cation channel thought to be involved in Ca(2+) reabsorption in kidney and intestine (PubMed:11549322, PubMed:18768590). Required for normal Ca(2+) reabsorption in the kidney distal convoluted tubules (By similarity). The channel is activated by low internal calcium level and the current exhibits an inward rectification (PubMed:11549322, PubMed:18768590). A Ca(2+)-dependent feedback regulation includes fast channel inactivation and slow current decay (By similarity). Heteromeric assembly with TRPV6 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating (By similarity).[UniProtKB:P69744][UniProtKB:Q9XSM3]<ref>PMID:11549322</ref> <ref>PMID:18768590</ref>
+[https://www.uniprot.org/uniprot/CALM1_HUMAN 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).<ref>PMID:16760425</ref> <ref>PMID:23893133</ref> <ref>PMID:26969752</ref> <ref>PMID:27165696</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 20: / Line 21: @@
 </div>
 <div class="pdbe-citations 5oeo" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Calmodulin 3D structures|Calmodulin 3D structures]]
+*[[Ion channels 3D structures|Ion channels 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Bate, N]]
+[[Category: Homo sapiens]]
-[[Category: Bokhovchuk, F M]]
+[[Category: Large Structures]]
-[[Category: Goult, B T]]
+[[Category: Bate N]]
-[[Category: Kovalevskaya, N]]
+[[Category: Bokhovchuk FM]]
-[[Category: Spronk, C A.E M]]
+[[Category: Goult BT]]
-[[Category: Vuister, G W]]
+[[Category: Kovalevskaya N]]
-[[Category: Calcium channel]]
+[[Category: Spronk CAEM]]
-[[Category: Calmodulin]]
+[[Category: Vuister GW]]
-[[Category: Dynamic]]
-[[Category: Membrane protein]]
-[[Category: Regulation]]
-[[Category: Trpv5]]

5oeo

From Proteopedia

Current revision

Solution structure of the complex of TRPV5(655-725) with a Calmodulin E32Q/E68Q double mutant

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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