1WPD

Evidence for domain-specific recognition of SK and Kv channels by MTX and HsTx1 scorpion toxins

Summary for 1WPD

• Entry DOI: 10.2210/pdb1wpd/pdb
• NMR Information: BMRB: 6347
• Descriptor: Potassium channel toxin alpha-KTx 6.2,Potassium channel toxin alpha-KTx 6.3 (1 entity in total)
• Functional Keywords: neurotoxin, chimera, toxin
• Biological source: Scorpio palmatus (Israeli golden scorpion); More
• Total number of polymer chains: 1
• Total formula weight: 3801.56

Authors

Regaya, I.,Beeton, C.,Ferrat, G.,Andreotti, N.,Chandy, G.K.,Darbon, H.,De Waard, M.,Sabatier, J.M. (deposition date: 2004-09-01, release date: 2004-10-19, Last modification date: 2024-10-16)

Primary citation

Regaya, I.,Beeton, C.,Ferrat, G.,Andreotti, N.,Darbon, H.,De Waard, M.,Sabatier, J.M.
Evidence for domain-specific recognition of SK and Kv channels by MTX and HsTx1 scorpion toxins
J.Biol.Chem., 279:55690-55696, 2004

PubMed Abstract: 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.

PubMed: 15498765
DOI: 10.1074/jbc.M410055200

Experimental method

SOLUTION NMR