7rnn
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 7rnn is ON HOLD Authors: Wu, Y., Chen, Z., Sigworth, F.J., Canessa, C.M. Description: human ASIC1a-Nb.C1 complex [[Category: Unreleased Structures]...) |
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| - | '''Unreleased structure''' | ||
| - | The entry | + | ==Human ASIC1a-Nb.C1 complex== |
| + | <StructureSection load='7rnn' size='340' side='right'caption='[[7rnn]], [[Resolution|resolution]] 2.86Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7rnn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RNN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RNN 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]] 2.86Å</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=7rnn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rnn OCA], [https://pdbe.org/7rnn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rnn RCSB], [https://www.ebi.ac.uk/pdbsum/7rnn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rnn 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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | ASIC1a is a proton-gated sodium channel involved in modulation of pain, fear, addiction, and ischemia-induced neuronal injury. We report isolation and characterization of alpaca-derived nanobodies (Nbs) that specifically target human ASIC1a. Cryo-electron microscopy of the human ASIC1a channel at pH 7.4 in complex with one of these, Nb.C1, yielded a structure at 2.9 A resolution. It is revealed that Nb.C1 binds to a site overlapping with that of the Texas coral snake toxin (MitTx1) and the black mamba venom Mambalgin-1; however, the Nb.C1-binding site does not overlap with that of the inhibitory tarantula toxin psalmotoxin-1 (PcTx1). Fusion of Nb.C1 with PcTx1 in a single polypeptide markedly enhances the potency of PcTx1, whereas competition of Nb.C1 and MitTx1 for binding reduces channel activation by the toxin. Thus, Nb.C1 is a molecular tool for biochemical and structural studies of hASIC1a; a potential antidote to the pain-inducing component of coral snake bite; and a candidate to potentiate PcTx1-mediated inhibition of hASIC1a in vivo for therapeutic applications. | ||
| - | + | Structure and analysis of nanobody binding to the human ASIC1a ion channel.,Wu Y, Chen Z, Sigworth FJ, Canessa CM Elife. 2021 Jul 28;10:e67115. doi: 10.7554/eLife.67115. PMID:34319232<ref>PMID:34319232</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Canessa | + | <div class="pdbe-citations 7rnn" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| - | [[Category: Sigworth | + | ==See Also== |
| - | [[Category: | + | *[[Ion channels 3D structures|Ion channels 3D structures]] |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Vicugna pacos]] | ||
| + | [[Category: Canessa CM]] | ||
| + | [[Category: Chen Z]] | ||
| + | [[Category: Sigworth FJ]] | ||
| + | [[Category: Wu Y]] | ||
Current revision
Human ASIC1a-Nb.C1 complex
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