8e0e
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==nbF3:CaV beta subunit 2a complex== | |
| + | <StructureSection load='8e0e' size='340' side='right'caption='[[8e0e]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8e0e]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Lama_glama Lama glama] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8E0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8E0E FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</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=8e0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8e0e OCA], [https://pdbe.org/8e0e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8e0e RCSB], [https://www.ebi.ac.uk/pdbsum/8e0e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8e0e ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/A0A8I6AEJ4_RAT A0A8I6AEJ4_RAT] The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.[ARBA:ARBA00002749] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Ca(2+) influx through high-voltage-activated calcium channels (HVACCs) controls diverse cellular functions. A critical feature enabling a singular signal, Ca(2+) influx, to mediate disparate functions is diversity of HVACC pore-forming alpha(1) and auxiliary Ca(V)beta(1)-Ca(V)beta(4) subunits. Selective Ca(V)alpha(1) blockers have enabled deciphering their unique physiological roles. By contrast, the capacity to post-translationally inhibit HVACCs based on Ca(V)beta isoform is non-existent. Conventional gene knockout/shRNA approaches do not adequately address this deficit owing to subunit reshuffling and partially overlapping functions of Ca(V)beta isoforms. Here, we identify a nanobody (nb.E8) that selectively binds Ca(V)beta(1) SH3 domain and inhibits Ca(V)beta(1)-associated HVACCs by reducing channel surface density, decreasing open probability, and speeding inactivation. Functionalizing nb.E8 with Nedd4L HECT domain yielded Chisel-1 which eliminated current through Ca(V)beta(1)-reconstituted Ca(V)1/Ca(V)2 and native Ca(V)1.1 channels in skeletal muscle, strongly suppressed depolarization-evoked Ca(2+) influx and excitation-transcription coupling in hippocampal neurons, but was inert against Ca(V)beta(2)-associated Ca(V)1.2 in cardiomyocytes. The results introduce an original method for probing distinctive functions of ion channel auxiliary subunit isoforms, reveal additional dimensions of Ca(V)beta(1) signaling in neurons, and describe a genetically-encoded HVACC inhibitor with unique properties. | ||
| - | + | Selective posttranslational inhibition of Ca(V)beta(1)-associated voltage-dependent calcium channels with a functionalized nanobody.,Morgenstern TJ, Nirwan N, Hernandez-Ochoa EO, Bibollet H, Choudhury P, Laloudakis YD, Ben Johny M, Bannister RA, Schneider MF, Minor DL Jr, Colecraft HM Nat Commun. 2022 Dec 9;13(1):7556. doi: 10.1038/s41467-022-35025-7. PMID:36494348<ref>PMID:36494348</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8e0e" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Lama glama]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Rattus norvegicus]] | ||
| + | [[Category: Minor DL]] | ||
| + | [[Category: Nirwan N]] | ||
Revision as of 07:33, 18 January 2023
nbF3:CaV beta subunit 2a complex
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