1hp2: Difference between revisions
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== | ==SOLUTION STRUCTURE OF A TOXIN FROM THE SCORPION TITYUS SERRULATUS (TSTX-K ALPHA) DETERMINED BY NMR.== | ||
<StructureSection load='1hp2' size='340' side='right'caption='[[1hp2]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1hp2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Tityus_serrulatus Tityus serrulatus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HP2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HP2 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1hp2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hp2 OCA], [https://pdbe.org/1hp2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hp2 RCSB], [https://www.ebi.ac.uk/pdbsum/1hp2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hp2 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/KAX41_TITSE KAX41_TITSE] Potently blocks Kv1.1/KCNA1 (85%), Kv1.2/KCNA2 (91%), Kv1.3/KCNA3 (89%), Kv1.6/KCNA6 (94%), and Shaker (97%).<ref>PMID:12871837</ref> <ref>PMID:24590385</ref> <ref>PMID:7509073</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
A toxin from the scorpion Tityus serrulatus (TsTX-Kalpha) blocks native squid K(+) channels and their cloned counterpart, sqKv1A, at pH 8 ((native)K(d) approximately 20 nM; (sqKv1A)K(d) approximately 10 nM). In both cases, decreasing the pH below 7.0 significantly diminishes the TsTX-Kalpha effect (pK = 6.6). In the cloned squid channel, the pH dependence of the block is abolished by a single point mutation (H351G), and no change in toxin affinity was observed at higher pH values (pH > or =8.0). To further investigate the TsTX-Kalpha-sqKv1A interaction, the three-dimensional structure of TsTX-Kalpha was determined in solution by NMR spectroscopy, and a model of the TsTX-Kalpha-sqKv1A complex was generated. As found for other alpha-K toxins such as charybdotoxin (CTX), site-directed mutagenesis at toxin residue K27 (K27A, K27R, and K27E) significantly reduced the toxin's affinity for sqKv1A channels. This is consistent with the TsTX-Kalpha-sqKv1A model reported here, which has K27 of the toxin inserted into the ion conduction pathway of the K(+) channel. This toxin-channel model also illustrates a possible mechanism for the pH-dependent block whereby lysine residues from TsTX-Kalpha (K6 and K23) are repelled by protonated H351 on sqKv1A at low pH. | A toxin from the scorpion Tityus serrulatus (TsTX-Kalpha) blocks native squid K(+) channels and their cloned counterpart, sqKv1A, at pH 8 ((native)K(d) approximately 20 nM; (sqKv1A)K(d) approximately 10 nM). In both cases, decreasing the pH below 7.0 significantly diminishes the TsTX-Kalpha effect (pK = 6.6). In the cloned squid channel, the pH dependence of the block is abolished by a single point mutation (H351G), and no change in toxin affinity was observed at higher pH values (pH > or =8.0). To further investigate the TsTX-Kalpha-sqKv1A interaction, the three-dimensional structure of TsTX-Kalpha was determined in solution by NMR spectroscopy, and a model of the TsTX-Kalpha-sqKv1A complex was generated. As found for other alpha-K toxins such as charybdotoxin (CTX), site-directed mutagenesis at toxin residue K27 (K27A, K27R, and K27E) significantly reduced the toxin's affinity for sqKv1A channels. This is consistent with the TsTX-Kalpha-sqKv1A model reported here, which has K27 of the toxin inserted into the ion conduction pathway of the K(+) channel. This toxin-channel model also illustrates a possible mechanism for the pH-dependent block whereby lysine residues from TsTX-Kalpha (K6 and K23) are repelled by protonated H351 on sqKv1A at low pH. | ||
Interaction of a toxin from the scorpion Tityus serrulatus with a cloned K+ channel from squid (sqKv1A).,Ellis KC, Tenenholz TC, Jerng H, Hayhurst M, Dudlak CS, Gilly WF, Blaustein MP, Weber DJ Biochemistry. 2001 May 22;40(20):5942-53. PMID:11352729<ref>PMID:11352729</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
[[Category: | <div class="pdbe-citations 1hp2" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Potassium channel toxin 3D structures|Potassium channel toxin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Tityus serrulatus]] | [[Category: Tityus serrulatus]] | ||
[[Category: Blaustein | [[Category: Blaustein MP]] | ||
[[Category: Ellis | [[Category: Ellis KC]] | ||
[[Category: Gilly | [[Category: Gilly WF]] | ||
[[Category: Tenenholz | [[Category: Tenenholz TC]] | ||
[[Category: Weber | [[Category: Weber DJ]] | ||
