Exploring structural features of the interaction between the scorpion toxinCnErg1 and ERG K+ channels.
The gamma-KTx-type scorpion toxins specific for K+ channels were found to interact with ERG channels on the turret region, while alpha-KTx3.2 Agitoxin-2 binds to the pore region of the Shaker K+ channel, and alpha-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 gamma-KTx binding, we determined the NMR structure of native gamma-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 1H-NMR three-dimensional solution structure of native ergtoxin (CnErg1) was solved using a total of 452 distance constraints, 13 3J(NH-Halpha) and 10 hydrogen bonds. The structure is characterized by 2 segments of alpha-helices and a triple-stranded antiparallel beta-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.
Frénal
Karine
K
Unité de RMN des Biomolécules URA 2185 CNRS, Institut Pasteur, Paris, France.
Xu
Chen-Qi
CQ
Wolff
Nicolas
N
Wecker
Karine
K
Gurrola
Georgina B
GB
Zhu
Shun-Yi
SY
Chi
Cheng-Wu
CW
Possani
Lourival D
LD
Tytgat
Jan
J
Delepierre
Muriel
M
D000595:Amino Acid Sequence; D000818:Animals; D016384:Consensus Sequence; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D019143:Evolution, Molecular; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010802:Phylogeny; D026902:Potassium Channel Blockers / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D015221:Potassium Channels / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D012604:Scorpion Venoms / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D016415:Sequence Alignment; D012984:Software; D013329:Structure-Activity Relationship
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012604:Scorpion Venoms; C118951:ergotoxin, Centruroides noxius; C087603:agitoxin 2