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5fdy

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Revision as of 12:42, 6 November 2017

Crystal structure of the Voltage-gated Sodium Channel Beta 2 subunit extracellular domain, C72A/C75A mutant

Structural highlights

5fdy is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	5feb
Gene:	SCN2B, UNQ326/PRO386 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[SCN2B_HUMAN] Familial atrial fibrillation. The disease is caused by mutations affecting the gene represented in this entry. Genetic variations in SCN2B may be involved in Brugada syndrome (PubMed:23559163). This tachyarrhythmia is characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset.^[1]

Function

[SCN2B_HUMAN] Crucial in the assembly, expression, and functional modulation of the heterotrimeric complex of the sodium channel. The subunit beta-2 causes an increase in the plasma membrane surface area and in its folding into microvilli. Interacts with TNR may play a crucial role in clustering and regulation of activity of sodium channels at nodes of Ranvier (By similarity).

Publication Abstract from PubMed

To investigate the mechanisms by which beta-subunits influence Nav channel function, we solved the crystal structure of the beta2 extracellular domain at 1.35A. We combined these data with known bacterial Nav channel structural insights and novel functional studies to determine the interactions of specific residues in beta2 with Nav1.2. We identified a flexible loop formed by (72)Cys and (75)Cys, a unique feature among the four beta-subunit isoforms. Moreover, we found that (55)Cys helps to determine the influence of beta2 on Nav1.2 toxin susceptibility. Further mutagenesis combined with the use of spider toxins reveals that (55)Cys forms a disulfide bond with (910)Cys in the Nav1.2 domain II pore loop, thereby suggesting a 1:1 stoichiometry. Our results also provide clues as to which disulfide bonds are formed between adjacent Nav1.2 (912/918)Cys residues. The concepts emerging from this work will help to form a model reflecting the beta-subunit location in a Nav channel complex.

Binary architecture of the Nav1.2-beta2 signaling complex.,Das S, Gilchrist J, Bosmans F, Van Petegem F Elife. 2016 Feb 19;5. pii: e10960. doi: 10.7554/eLife.10960. PMID:26894959^[2]

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

References

↑ Riuro H, Beltran-Alvarez P, Tarradas A, Selga E, Campuzano O, Verges M, Pagans S, Iglesias A, Brugada J, Brugada P, Vazquez FM, Perez GJ, Scornik FS, Brugada R. A missense mutation in the sodium channel beta2 subunit reveals SCN2B as a new candidate gene for Brugada syndrome. Hum Mutat. 2013 Jul;34(7):961-6. doi: 10.1002/humu.22328. Epub 2013 Apr 29. PMID:23559163 doi:http://dx.doi.org/10.1002/humu.22328
↑ Das S, Gilchrist J, Bosmans F, Van Petegem F. Binary architecture of the Nav1.2-beta2 signaling complex. Elife. 2016 Feb 19;5. pii: e10960. doi: 10.7554/eLife.10960. PMID:26894959 doi:http://dx.doi.org/10.7554/eLife.10960

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5fdy"

@@ Line 3: / Line 3: @@
 <StructureSection load='5fdy' size='340' side='right' caption='[[5fdy]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5fdy]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FDY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FDY FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5fdy]] is a 2 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=5FDY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FDY FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5feb|5feb]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SCN2B, UNQ326/PRO386 ([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=5fdy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fdy OCA], [http://pdbe.org/5fdy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fdy RCSB], [http://www.ebi.ac.uk/pdbsum/5fdy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fdy ProSAT]</span></td></tr>
 </table>
@@ Line 25: / Line 26: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Das, S]]
 [[Category: Petegem, F Van]]

5fdy

From Proteopedia

Revision as of 12:42, 6 November 2017

Crystal structure of the Voltage-gated Sodium Channel Beta 2 subunit extracellular domain, C72A/C75A mutant

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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