4l1d: Difference between revisions
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==Voltage-gated sodium channel beta3 subunit Ig domain== | ==Voltage-gated sodium channel beta3 subunit Ig domain== | ||
<StructureSection load='4l1d' size='340' side='right' caption='[[4l1d]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='4l1d' size='340' side='right'caption='[[4l1d]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
[[4l1d]] is a 3 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4l1d]] 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=4L1D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4L1D 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]] 2.5Å</td></tr> | ||
<b> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4l1d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l1d OCA], [https://pdbe.org/4l1d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4l1d RCSB], [https://www.ebi.ac.uk/pdbsum/4l1d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4l1d ProSAT]</span></td></tr> | ||
</table> | |||
== Disease == | == Disease == | ||
[ | [https://www.uniprot.org/uniprot/SCN3B_HUMAN SCN3B_HUMAN] Brugada syndrome. The disease is caused by mutations affecting the gene represented in this entry. | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/SCN3B_HUMAN SCN3B_HUMAN] Modulates channel gating kinetics. Causes unique persistent sodium currents. Inactivates the sodium channel opening more slowly than the subunit beta-1. Its association with neurofascin may target the sodium channels to the nodes of Ranvier of developing axons and retain these channels at the nodes in mature myelinated axons (By similarity). | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
The vertebrate sodium (Nav) channel is composed of an ion-conducting alpha subunit and associated beta subunits. Here, we report the crystal structure of the human beta3 subunit immunoglobulin (Ig) domain, a functionally important component of Nav channels in neurons and cardiomyocytes. Surprisingly, we found that the beta3 subunit Ig domain assembles as a trimer in the crystal asymmetric unit. Analytical ultracentrifugation confirmed the presence of Ig domain monomers, dimers, and trimers in free solution, and atomic force microscopy imaging also detected full-length beta3 subunit monomers, dimers, and trimers. Mutation of a cysteine residue critical for maintaining the trimer interface destabilized both dimers and trimers. Using fluorescence photoactivated localization microscopy, we detected full-length beta3 subunit trimers on the plasma membrane of transfected HEK293 cells. We further show that beta3 subunits can bind to more than one site on the Nav 1.5 alpha subunit and induce the formation of alpha subunit oligomers, including trimers. Our results suggest a new and unexpected role for the beta3 subunits in Nav channel cross-linking and provide new structural insights into some pathological Nav channel mutations. | The vertebrate sodium (Nav) channel is composed of an ion-conducting alpha subunit and associated beta subunits. Here, we report the crystal structure of the human beta3 subunit immunoglobulin (Ig) domain, a functionally important component of Nav channels in neurons and cardiomyocytes. Surprisingly, we found that the beta3 subunit Ig domain assembles as a trimer in the crystal asymmetric unit. Analytical ultracentrifugation confirmed the presence of Ig domain monomers, dimers, and trimers in free solution, and atomic force microscopy imaging also detected full-length beta3 subunit monomers, dimers, and trimers. Mutation of a cysteine residue critical for maintaining the trimer interface destabilized both dimers and trimers. Using fluorescence photoactivated localization microscopy, we detected full-length beta3 subunit trimers on the plasma membrane of transfected HEK293 cells. We further show that beta3 subunits can bind to more than one site on the Nav 1.5 alpha subunit and induce the formation of alpha subunit oligomers, including trimers. Our results suggest a new and unexpected role for the beta3 subunits in Nav channel cross-linking and provide new structural insights into some pathological Nav channel mutations. | ||
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Crystal Structure and Molecular Imaging of the Nav Channel beta3 Subunit Indicates a Trimeric Assembly.,Namadurai S, Balasuriya D, Rajappa R, Wiemhofer M, Stott K, Klingauf J, Edwardson JM, Chirgadze DY, Jackson AP J Biol Chem. 2014 Apr 11;289(15):10797-811. doi: 10.1074/jbc.M113.527994. Epub, 2014 Feb 24. PMID:24567321<ref>PMID:24567321</ref> | Crystal Structure and Molecular Imaging of the Nav Channel beta3 Subunit Indicates a Trimeric Assembly.,Namadurai S, Balasuriya D, Rajappa R, Wiemhofer M, Stott K, Klingauf J, Edwardson JM, Chirgadze DY, Jackson AP J Biol Chem. 2014 Apr 11;289(15):10797-811. doi: 10.1074/jbc.M113.527994. Epub, 2014 Feb 24. PMID:24567321<ref>PMID:24567321</ref> | ||
From | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
<div class="pdbe-citations 4l1d" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Ion channels 3D structures|Ion channels 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Chirgadze | [[Category: Large Structures]] | ||
[[Category: Jackson | [[Category: Chirgadze DY]] | ||
[[Category: Klingauf | [[Category: Jackson AP]] | ||
[[Category: Namadurai | [[Category: Klingauf J]] | ||
[[Category: Rajappa | [[Category: Namadurai S]] | ||
[[Category: Stott | [[Category: Rajappa R]] | ||
[[Category: Weimhofer | [[Category: Stott K]] | ||
[[Category: Weimhofer M]] | |||