Solution structure of maurotoxin, a scorpion toxin fromScorpio maurus, with high affinity for voltage-gated potassium channels

Abstract

Maurotoxin (MTX), purified from the scorpionid Scorpio maurus is a potent ligand for potassium channels. It shows a broad specificity as being active on Kv1.1 (Kd = 37 nM), Kv1.2 (Kd = 0.8 nM), Kv1.3 (Kd = 150 nM) voltage-gated potassium channels, as well as on small-conductance calcium-activated potassium channels. It has a unique disulfide pairing among the scorpion toxins family. The solution structure of MTX has been determined by 2D-NMR techniques, which led to the full description of its 3D conformation: a bended helix from residues 6 to 16 connected by a loop to a two-stranded antiparallel beta sheet (residues 23 to 26 and 28 to 31). The interaction of MTX with the pore region of the Kv1.2 potassium channel has been modeled according to their charge anisotropy. The structure of MTX is similar to other short scorpion toxins despite its peculiar disulfide pairing. Its interaction with the Kv1.2 channel involves a dipole moment, which guides and orients the toxin onto the pore, toward the binding site, and which thus is responsible for the specificity.

Establishing a reference array for the CS-αβ superfamily of defensive peptides

“…Some eight-cysteine potassium-channel toxins from scorpions are also consistent with the mollusk/nematode cysteine pattern and structure (represented by Maurotoxin, Fig. 1a, k) [37]. Since there doesn’t seem to be a consensus that “defensin” should apply only to six-cysteine sequences, there seems to be no reason that nematode “antibacterial factors” could not be referred to as “nematode defensins.”…”

Structural Basis of the Selective Block of Kv1.2 by Maurotoxin from Computer Simulations

“…After the 5-ns equilibration, we place MTx (PDB ID 1TXM [32]) into each simulation box, ∼15 Å above the position where the toxin is fully bound. A flat-bottom harmonic distance restraint is applied between the side chain nitrogen atom of MTx-Lys23 and the carbonyl group of the channel residue Gly376.…”

“…(A) The secondary structure of MTx (PDB ID 1TXM [32]). α-Helix is shown in purple and β-sheets in yellow.…”

CHAPTER 2. The Structural Universe of Disulfide-Rich Venom Peptides

“…157 The a-KTx6.2, also known as maurotoxin (Figure 2.11B), from the venom of the chactoid scorpion Scorpio maurus palmatus is a 34-residue peptide comprising an eight-cysteine scaffold (C-C-C-C-C-C-C-C) with disulde connectivity C I -C V , C II -C VI , C III -C IV , C VII -C VIII . [159][160][161][162][163] The C I -C V , C II -C VI , and C III -C IV disulde bonds constitute the core disulde framework found in CSa/b defensins, with the C-terminal C VII -C VIII disulde being an elaboration of the core fold. The core CSa/b fold is comprised of a single a-helix (Ser6-Gln16) abutting a two-stranded antiparallel b-sheet (b-strands Lys23-Asn26 and Ser28-Cys31).…”

“…The core CSa/b fold is comprised of a single a-helix (Ser6-Gln16) abutting a two-stranded antiparallel b-sheet (b-strands Lys23-Asn26 and Ser28-Cys31). 163 …”