1wpd
From Proteopedia
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'''Evidence for domain-specific recognition of SK and Kv channels by MTX and HsTx1 scorpion toxins''' | '''Evidence for domain-specific recognition of SK and Kv channels by MTX and HsTx1 scorpion toxins''' | ||
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[[Category: Sabatier, J M.]] | [[Category: Sabatier, J M.]] | ||
[[Category: Waard, M De.]] | [[Category: Waard, M De.]] | ||
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| - | [[Category: | + | [[Category: Neurotoxin]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 13:58:44 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 10:58, 3 May 2008
Evidence for domain-specific recognition of SK and Kv channels by MTX and HsTx1 scorpion toxins
Overview
Maurotoxin (MTX) and HsTx1 are two scorpion toxins belonging to the alpha-KTx6 structural family. These 34-residue toxins, cross-linked by four disulfide bridges, share 59% sequence identity and fold along the classical alpha/beta scaffold. Despite these structural similarities, they fully differ in their pharmacological profiles. MTX is highly active on small (SK) and intermediate (IK) conductance Ca(2+)-activated (K(+)) channels and on voltage-gated Kv1.2 channel, whereas HsTx1 potently blocks voltage-gated Kv1.1 and Kv1.3 channels only. Here, we designed and chemically produced MTX-HsTx1, a chimera of both toxins that contains the N-terminal helical region of MTX (sequence 1-16) and the C-terminal beta-sheet region of HsTx1 (sequence 17-34). The three-dimensional structure of the peptide in solution was solved by (1)H NMR. MTX-HsTx1 displays the activity of MTX on SK channel, whereas it exhibits the pharmacological profile of HsTx1 on Kv1.1, Kv1.2, Kv1.3, and IK channels. These data demonstrate that the helical region of MTX exerts a key role in SK channel recognition, whereas the beta-sheet region of HsTx1 is crucial for activity on all other channel types tested.
About this Structure
1WPD is a Single protein structure of sequence from Scorpio maurus palmatus and heterometrus spinifer. Full crystallographic information is available from OCA.
Reference
Evidence for domain-specific recognition of SK and Kv channels by MTX and HsTx1 scorpion toxins., Regaya I, Beeton C, Ferrat G, Andreotti N, Darbon H, De Waard M, Sabatier JM, J Biol Chem. 2004 Dec 31;279(53):55690-6. Epub 2004 Oct 21. PMID:15498765 Page seeded by OCA on Sat May 3 13:58:44 2008
