6j8e
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | The entry | + | ==Human Nav1.2-beta2-KIIIA ternary complex== |
| + | <StructureSection load='6j8e' size='340' side='right' caption='[[6j8e]], [[Resolution|resolution]] 3.00Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6j8e]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6J8E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6J8E FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9Z9:(3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]spirost-5-en'>9Z9</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6j8e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6j8e OCA], [http://pdbe.org/6j8e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6j8e RCSB], [http://www.ebi.ac.uk/pdbsum/6j8e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6j8e ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/SCN2B_HUMAN 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.<ref>PMID:23559163</ref> [[http://www.uniprot.org/uniprot/SCN2A_HUMAN SCN2A_HUMAN]] Defects in SCN2A are the cause of seizures, benign familial infantile type 3 (BFIS3) [MIM:[http://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:[http://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> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/SCN2B_HUMAN 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). [[http://www.uniprot.org/uniprot/CM3A_CONKI CM3A_CONKI]] Mu-conotoxins block voltage-gated sodium channels (Nav). This toxin potently blocks rNav1.2/SCN2A and rNav1.4/SCN4A. It also moderately blocks rNav1.1/SCN1A, rNav1.3/SCN3A, rNav1.5/SCN5A, mNav1.6/SCN8A, and rNav1.7/SCN9A. On rNav1.2/SCN2A, it produces a block that is only partially reversible. The block of SCN9A is modified when beta-subunits are coexpressed with the alpha subunit. Hence, blocks of channels containing beta-1 and beta-3 subunits are more potent (compared to channels without beta subunits), whereas blocks of channels containing beta-2 and beta-4 subunits are less potent (compared to channels without beta subunits).<ref>PMID:15882064</ref> <ref>PMID:17724025</ref> <ref>PMID:18950653</ref> <ref>PMID:21652775</ref> <ref>PMID:21709136</ref> <ref>PMID:21781281</ref> <ref>PMID:23146020</ref> [[http://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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The voltage-gated sodium channel Nav1.2 is responsible for the initiation and propagation of action potentials in the central nervous system. We report the cryo-electron microscopy structure of human Nav1.2 bound to a peptidic pore blocker, the mu-conotoxin KIIIA, in the presence of an auxiliary subunit beta2 to an overall resolution of 3.0 A. The immunoglobulin (Ig) domain of beta2 interacts with the shoulder of the pore domain through a disulfide bond. The 16-residue KIIIA interacts with the extracellular segments in repeats I to III, placing Lys7 at the entrance to the selectivity filter. Many interacting residues are specific to Nav1.2, revealing a molecular basis for KIIIA specificity. The structure establishes a framework for rational design of subtype-specific blockers for Nav channels. | ||
| - | + | Molecular basis for pore blockade of human Na(+) channel Nav1.2 by the mu-conotoxin KIIIA.,Pan X, Li Z, Huang X, Huang G, Gao S, Shen H, Liu L, Lei J, Yan N Science. 2019 Feb 14. pii: science.aaw2999. doi: 10.1126/science.aaw2999. PMID:30765605<ref>PMID:30765605</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6j8e" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Huang, G]] | ||
| + | [[Category: Huang, X]] | ||
| + | [[Category: Li, Z]] | ||
| + | [[Category: Pan, X]] | ||
| + | [[Category: Yan, N]] | ||
| + | [[Category: Membrane protein]] | ||
| + | [[Category: Membrane protein-toxin complex]] | ||
| + | [[Category: Transmembrane protein]] | ||
Revision as of 15:27, 27 February 2019
Human Nav1.2-beta2-KIIIA ternary complex
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