New binding site on common molecular scaffold provides HERG channel specificity of scorpion toxin BeKm-1.

TY - JOUR

T1 - New binding site on common molecular scaffold provides HERG channel specificity of scorpion toxin BeKm-1.

AU - Korolkova, Yuliya V

AU - Bocharov, Eduard V

AU - Angelo, Kamilla

AU - Maslennikov, Innokenty V

AU - Grinenko, Olga V

AU - Lipkin, Aleksey V

AU - Nosyreva, Elena D

AU - Pluzhnikov, Kirill A

AU - Olesen, Søren-Peter

AU - Arseniev, Alexander S

AU - Grishin, Eugene V

N1 - Keywords: Amino Acid Sequence; Binding Sites; Cation Transport Proteins; DNA-Binding Proteins; Ether-A-Go-Go Potassium Channels; Humans; Models, Molecular; Molecular Sequence Data; Plasmids; Potassium Channels; Potassium Channels, Voltage-Gated; Protein Conformation; Protein Structure, Secondary; Protein Subunits; Recombinant Proteins; Scorpion Venoms; Sequence Alignment; Sequence Homology, Amino Acid; Solutions; Substrate Specificity; Trans-Activators

PY - 2002

Y1 - 2002

N2 - The scorpion toxin BeKm-1 is unique among a variety of known short scorpion toxins affecting potassium channels in its selective action on ether-a-go-go-related gene (ERG)-type channels. BeKm-1 shares the common molecular scaffold with other short scorpion toxins. The toxin spatial structure resolved by NMR consists of a short alpha-helix and a triple-stranded antiparallel beta-sheet. By toxin mutagenesis study we identified the residues that are important for the binding of BeKm-1 to the human ERG K+ (HERG) channel. The most critical residues (Tyr-11, Lys-18, Arg-20, Lys-23) are located in the alpha-helix and following loop whereas the "traditional" functional site of other short scorpion toxins is formed by residues from the beta-sheet. Thus the unique location of the binding site of BeKm-1 provides its specificity toward the HERG channel.

AB - The scorpion toxin BeKm-1 is unique among a variety of known short scorpion toxins affecting potassium channels in its selective action on ether-a-go-go-related gene (ERG)-type channels. BeKm-1 shares the common molecular scaffold with other short scorpion toxins. The toxin spatial structure resolved by NMR consists of a short alpha-helix and a triple-stranded antiparallel beta-sheet. By toxin mutagenesis study we identified the residues that are important for the binding of BeKm-1 to the human ERG K+ (HERG) channel. The most critical residues (Tyr-11, Lys-18, Arg-20, Lys-23) are located in the alpha-helix and following loop whereas the "traditional" functional site of other short scorpion toxins is formed by residues from the beta-sheet. Thus the unique location of the binding site of BeKm-1 provides its specificity toward the HERG channel.

U2 - 10.1074/jbc.M204083200

DO - 10.1074/jbc.M204083200

M3 - Journal article

C2 - 12151390

SN - 0021-9258

VL - 277

SP - 43104

EP - 43109

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 45

ER -