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Exploring structural features of the interaction between the scorpion toxinCnErg1 and ERG K + channels
Author(s) -
Frénal Karine,
Xu ChenQi,
Wolff Nicolas,
Wecker Karine,
Gurrola Georgina B.,
Zhu ShunYi,
Chi ChengWu,
Possani Lourival D.,
Tytgat Jan,
Delepierre Muriel
Publication year - 2004
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.20102
Subject(s) - scorpion toxin , scorpion , antiparallel (mathematics) , chemistry , stereochemistry , amino acid , crystallography , protein structure , venom , biochemistry , physics , quantum mechanics , magnetic field
The γ‐KTx–type scorpion toxins specific for K + channels were found to interact with ERG channels on the turret region, while α‐KTx3.2 Agitoxin‐2 binds to the pore region of the Shaker K + channel, and α‐KTx5.3 BmP05 binds to the intermediate region of the small‐conductance calcium‐activated K‐channel (SK Ca ). In order to explore the critical residues for γ‐KTx binding, we determined the NMR structure of native γ‐KTx1.1 (CnErg1), a 42 amino acid residues scorpion toxin isolated from the venom of the Mexican scorpion Centruroïdes noxius Hoffmann, and we used computational evolutionary trace (ET) analysis to predict possible structural and functional features of interacting surfaces. The 1 H‐NMR three‐dimensional solution structure of native ergtoxin (CnErg1) was solved using a total of 452 distance constraints, 13 3 J NH‐Hα and 10 hydrogen bonds. The structure is characterized by 2 segments of α‐helices and a triple‐stranded antiparallel β‐sheet stabilized by 4 disulfide bridges. The ET and structural analysis provided indication of the presence of two important amino acid residue clusters, one hydrophobic and the other hydrophilic, that should be involved in the surface contact between the toxin and the channel. Some features of the proposed interacting surface are discussed. Proteins 2004. © 2004 Wiley‐Liss, Inc.