1hp2: Difference between revisions
New page: left|200px<br /><applet load="1hp2" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hp2" /> '''SOLUTION STRUCTURE OF A TOXIN FROM THE SCORP... |
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[[Image:1hp2.jpg|left|200px]]<br /><applet load="1hp2" size=" | [[Image:1hp2.jpg|left|200px]]<br /><applet load="1hp2" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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'''SOLUTION STRUCTURE OF A TOXIN FROM THE SCORPION TITYUS SERRULATUS (TSTX-K ALPHA) DETERMINED BY NMR.'''<br /> | '''SOLUTION STRUCTURE OF A TOXIN FROM THE SCORPION TITYUS SERRULATUS (TSTX-K ALPHA) DETERMINED BY NMR.'''<br /> | ||
==Overview== | ==Overview== | ||
A toxin from the scorpion Tityus serrulatus (TsTX-Kalpha) blocks native | 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. | ||
==About this Structure== | ==About this Structure== | ||
1HP2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Tityus_serrulatus Tityus serrulatus]. Full crystallographic information is available from [http:// | 1HP2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Tityus_serrulatus Tityus serrulatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HP2 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Tityus serrulatus]] | [[Category: Tityus serrulatus]] | ||
[[Category: Blaustein, M | [[Category: Blaustein, M P.]] | ||
[[Category: Ellis, K | [[Category: Ellis, K C.]] | ||
[[Category: Gilly, W | [[Category: Gilly, W F.]] | ||
[[Category: Tenenholz, T | [[Category: Tenenholz, T C.]] | ||
[[Category: Weber, D | [[Category: Weber, D J.]] | ||
[[Category: alpha-k toxin]] | [[Category: alpha-k toxin]] | ||
[[Category: k+ channel]] | [[Category: k+ channel]] | ||
[[Category: scorpion toxin]] | [[Category: scorpion toxin]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:03:31 2008'' | ||
Revision as of 14:03, 21 February 2008
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SOLUTION STRUCTURE OF A TOXIN FROM THE SCORPION TITYUS SERRULATUS (TSTX-K ALPHA) DETERMINED BY NMR.
OverviewOverview
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.
About this StructureAbout this Structure
1HP2 is a Single protein structure of sequence from Tityus serrulatus. Full crystallographic information is available from OCA.
ReferenceReference
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
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