View source for 7cft


==Cryo-EM strucutre of human acid-sensing ion channel 1a in complex with snake toxin Mambalgin1 at pH 8.0==
<StructureSection load='7cft' size='340' side='right'caption='[[7cft]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7cft]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Dendroaspis_polylepis_polylepis Dendroaspis polylepis polylepis] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CFT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CFT 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]] 3.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=7cft FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cft OCA], [https://pdbe.org/7cft PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cft RCSB], [https://www.ebi.ac.uk/pdbsum/7cft PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cft ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ASIC1_HUMAN ASIC1_HUMAN] Isoform 2 and isoform 3 function as proton-gated sodium channels; they are activated by a drop of the extracellular pH and then become rapidly desensitized. The channel generates a biphasic current with a fast inactivating and a slow sustained phase. Has high selectivity for sodium ions and can also transport lithium ions with high efficiency. Isoform 2 can also transport potassium, but with lower efficiency. It is nearly impermeable to the larger rubidium and cesium ions. Isoform 3 can also transport calcium ions. Mediates glutamate-independent Ca(2+) entry into neurons upon acidosis. This Ca(2+) overloading is toxic for cortical neurons and may be in part responsible for ischemic brain injury. Heteromeric channel assembly seems to modulate channel properties. Functions as a postsynaptic proton receptor that influences intracellular Ca(2+) concentration and calmodulin-dependent protein kinase II phosphorylation and thereby the density of dendritic spines. Modulates activity in the circuits underlying innate fear.<ref>PMID:22760635</ref>   Isoform 1 does not display proton-gated cation channel activity.<ref>PMID:22760635</ref> 
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== Publication Abstract from PubMed ==
Acid-sensing ion channels (ASICs) are proton-gated cation channels that are involved in diverse neuronal processes including pain sensing. The peptide toxin Mambalgin1 (Mamba1) from black mamba snake venom can reversibly inhibit the conductance of ASICs, causing an analgesic effect. However, the detailed mechanism by which Mamba1 inhibits ASIC1s, especially how Mamba1 binding to the extracellular domain affects the conformational changes of the transmembrane domain of ASICs remains elusive. Here, we present single-particle cryo-EM structures of human ASIC1a (hASIC1a) and the hASIC1a-Mamba1 complex at resolutions of 3.56 and 3.90 A, respectively. The structures revealed the inhibited conformation of hASIC1a upon Mamba1 binding. The combination of the structural and physiological data indicates that Mamba1 preferentially binds hASIC1a in a closed state and reduces the proton sensitivity of the channel, representing a closed-state trapping mechanism.

Structural insights into human acid-sensing ion channel 1a inhibition by snake toxin mambalgin1.,Sun D, Liu S, Li S, Zhang M, Yang F, Wen M, Shi P, Wang T, Pan M, Chang S, Zhang X, Zhang L, Tian C, Liu L Elife. 2020 Sep 11;9. pii: 57096. doi: 10.7554/eLife.57096. PMID:32915133<ref>PMID:32915133</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7cft" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ion channels 3D structures|Ion channels 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Dendroaspis polylepis polylepis]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Li SY]]
[[Category: Liu SL]]
[[Category: Sun DM]]
[[Category: Tian CL]]
[[Category: Yang F]]