6but

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==Solution structure of full-length apo mammalian calmodulin bound to the IQ motif of the human voltage-gated sodium channel NaV1.2==
==Solution structure of full-length apo mammalian calmodulin bound to the IQ motif of the human voltage-gated sodium channel NaV1.2==
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<StructureSection load='6but' size='340' side='right'caption='[[6but]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
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<StructureSection load='6but' size='340' side='right'caption='[[6but]]' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6but]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BUT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BUT FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6but]] 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=6BUT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BUT FirstGlance]. <br>
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</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CALM1, CALM, CAM, CAM1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SCN2A, NAC2, SCN2A1, SCN2A2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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</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'>[https://proteopedia.org/fgij/fg.htm?mol=6but FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6but OCA], [https://pdbe.org/6but PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6but RCSB], [https://www.ebi.ac.uk/pdbsum/6but PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6but ProSAT]</span></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=6but FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6but OCA], [https://pdbe.org/6but PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6but RCSB], [https://www.ebi.ac.uk/pdbsum/6but PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6but ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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[[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. [[https://www.uniprot.org/uniprot/SCN2A_HUMAN SCN2A_HUMAN]] Defects in SCN2A are the cause of seizures, benign familial infantile type 3 (BFIS3) [MIM:[https://omim.org/entry/607745 607745]]. An autosomal dominant disorder in which afebrile seizures occur in clusters during the first year of life, without neurologic sequelae.<ref>PMID:11371648</ref> <ref>PMID:12243921</ref> <ref>PMID:15048894</ref> <ref>PMID:20371507</ref> Defects in SCN2A are the cause of epileptic encephalopathy early infantile type 11 (EIEE11) [MIM:[https://omim.org/entry/613721 613721]]. EIEE11 is an autosomal dominant seizure disorder characterized by infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities.<ref>PMID:19786696</ref> <ref>PMID:20956790</ref>
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[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 ==
== Function ==
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[[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> [[https://www.uniprot.org/uniprot/SCN2A_HUMAN SCN2A_HUMAN]] Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Neuronal voltage-gated sodium channel NaV1.2 C-terminal domain (CTD) binds calmodulin (CaM) constitutively at its IQ motif. A solution structure (6BUT) and other NMR evidence showed that the CaM N domain (CaMN) is structurally independent of the C-domain (CaMC) whether CaM is bound to the NaV1.2IQp (1,901-1,927) or NaV1.2CTD (1,777-1,937) with or without calcium. However, in the CaM + NaV1.2CTD complex, the Ca(2+) affinity of CaMN was more favorable than in free CaM, while Ca(2+) affinity for CaMC was weaker than in the CaM + NaV1.2IQp complex. The CTD EF-like (EFL) domain allosterically widened the energetic gap between CaM domains. Cardiomyopathy-associated CaM mutants (N53I(N54I), D95V(D96V), A102V(A103V), E104A(E105A), D129G(D130G), and F141L(F142L)) all bound the NaV1.2 IQ motif favorably under resting (apo) conditions and bound calcium normally at CaMN sites. However, only N53I and A102V bound calcium at CaMC sites at [Ca(2+)] &lt; 100 muM. Thus, they are expected to respond like wild-type CaM to Ca(2+) spikes in excitable cells.
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NaV1.2 EFL domain allosterically enhances Ca(2+) binding to sites I and II of WT and pathogenic calmodulin mutants bound to the channel CTD.,Mahling R, Hovey L, Isbell HM, Marx DC, Miller MS, Kilpatrick AM, Weaver LD, Yoder JB, Kim EH, Andresen CNJ, Li S, Shea MA Structure. 2021 Mar 23. pii: S0969-2126(21)00075-7. doi:, 10.1016/j.str.2021.03.002. PMID:33770503<ref>PMID:33770503</ref>
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==See Also==
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*[[Calmodulin 3D structures|Calmodulin 3D structures]]
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6but" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Kilpatrick, A M]]
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[[Category: Kilpatrick AM]]
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[[Category: Mahling, R]]
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[[Category: Mahling R]]
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[[Category: Shea, M A]]
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[[Category: Shea MA]]
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[[Category: Calcium-binding protein]]
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[[Category: Membrane protein]]
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[[Category: Metal transport ion channel neuronal molecular recognition]]
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Current revision

Solution structure of full-length apo mammalian calmodulin bound to the IQ motif of the human voltage-gated sodium channel NaV1.2

PDB ID 6but

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