7rnn: Difference between revisions
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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]] | |||