6j8h

From Proteopedia

(Difference between revisions)

Current revision

Structure of human voltage-gated sodium channel Nav1.7 in complex with auxiliary beta subunits, huwentoxin-IV and saxitoxin (Y1755 down)

6j8h, resolution 3.20Å

Structural highlights

6j8h 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:	Electron Microscopy, Resolution 3.2Å
Ligands:
Experimental data:	Check to display Experimental Data
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

Voltage-gated sodium channel Nav1.7 represents a promising target for pain relief. Here we report the cryo-EM structures of the human Nav1.7-beta1-beta2 complex bound to two combinations of pore blockers and gating modifier toxins (GMTs), tetrodotoxin with Protoxin-II and saxitoxin with Huwentoxin-IV, both determined at overall resolutions of 3.2 A. The two structures are nearly identical except for minor shifts of VSDII, whose S3-S4 linker accommodates the two GMTs in a similar manner. One additional Protoxin-II sits on top of the S3-S4 linker in VSDIV The structures may represent an inactivated state with all four VSDs "up" and the intracellular gate closed. The structures illuminate the path toward mechanistic understanding of the function and disease of Nav1.7 and establish the foundation for structure-aided development of analgesics.

Structures of human Nav1.7 channel in complex with auxiliary subunits and animal toxins.,Shen H, Liu D, Wu K, Lei J, Yan N Science. 2019 Feb 14. pii: science.aaw2493. doi: 10.1126/science.aaw2493. PMID:30765606^[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
↑ Shen H, Liu D, Wu K, Lei J, Yan N. Structures of human Nav1.7 channel in complex with auxiliary subunits and animal toxins. Science. 2019 Feb 14. pii: science.aaw2493. doi: 10.1126/science.aaw2493. PMID:30765606 doi:http://dx.doi.org/10.1126/science.aaw2493

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/6j8h"

@@ Line 5: / Line 5: @@
 <table><tr><td colspan='2'>[[6j8h]] 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=6J8H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6J8H FirstGlance]. <br>
 </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
-<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9SL:[(3aS,4R,10aS)-2,6-diamino-10,10-dihydroxy-3a,4,9,10-tetrahydro-3H,8H-pyrrolo[1,2-c]purin-4-yl]methyl+carbamate'>9SL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9SL:[(3~{a}~{S},4~{R},10~{a}~{S})-2,6-bis(azanyl)-10,10-bis(oxidanyl)-3~{a},4,8,9-tetrahydro-3~{H}-pyrrolo[1,2-c]purin-4-yl]methyl+carbamate'>9SL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=6j8h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6j8h OCA], [https://pdbe.org/6j8h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6j8h RCSB], [https://www.ebi.ac.uk/pdbsum/6j8h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6j8h ProSAT]</span></td></tr>
 </table>

6j8h

From Proteopedia

Current revision

Structure of human voltage-gated sodium channel Nav1.7 in complex with auxiliary beta subunits, huwentoxin-IV and saxitoxin (Y1755 down)

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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