1hp2
From Proteopedia
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'''SOLUTION STRUCTURE OF A TOXIN FROM THE SCORPION TITYUS SERRULATUS (TSTX-K ALPHA) DETERMINED BY NMR.''' | '''SOLUTION STRUCTURE OF A TOXIN FROM THE SCORPION TITYUS SERRULATUS (TSTX-K ALPHA) DETERMINED BY NMR.''' | ||
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[[Category: Tenenholz, T C.]] | [[Category: Tenenholz, T C.]] | ||
[[Category: Weber, D J.]] | [[Category: Weber, D J.]] | ||
| - | [[Category: | + | [[Category: Alpha-k toxin]] |
| - | [[Category: | + | [[Category: K+ channel]] |
| - | [[Category: | + | [[Category: Scorpion toxin]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 19:04:59 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 16:05, 2 May 2008
SOLUTION STRUCTURE OF A TOXIN FROM THE SCORPION TITYUS SERRULATUS (TSTX-K ALPHA) DETERMINED BY NMR.
Overview
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
1HP2 is a Single protein structure of sequence from Tityus serrulatus. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Fri May 2 19:04:59 2008
