Determination of the three-dimensional solution structure of noxiustoxin: analysis of structural differences with related short-chain scorpion toxins.
The 3D structure of noxiustoxin, the first identified scorpion toxin acting on K+ channels, has been elucidated by NMR and molecular modeling. Thirty-nine solution structures were calculated using 572 distance and 42 dihedral restraints. The average atomic rms deviation between the refined structures and the mean structure is 0.75 A for the backbone atoms. Noxiustoxin adopts a alpha/beta scaffold constituted of a three-stranded beta-sheet (residues 2-3, 25-30, 33-38) linked to a helix (residues 10-20) through two disulfide bridges. A comparison between the 3D structure of noxiustoxin and those of other structurally and functionally related scorpion toxins (charybdotoxin, PO5-NH2, kaliotoxin) revealed a bending capacity of the helix and a variability in the relative orientations between the helix and the beta-sheet. These two features highlight the plasticity of the alpha/beta scaffold and offer a structural explanation for the capacity of the fold to accommodate an additional alanine residue in the Gly-x-Cys pattern of a previously proposed consensus sequence [Bontems et al. (1991) Science 254, 1521-1523]. Our structural data also emphasize the possibility that the beta-sheet of NTX is implicated in the capacity of NTX to recognize voltage-dependent K+ channels.
Dauplais
M
M
Département d'Ingénierie et d'Etude des Protéines, CE-Saclay, Gif-sur-Yvette, France.
Gilquin
B
B
Possani
L D
LD
Gurrola-Briones
G
G
Roumestand
C
C
Ménez
A
A
D000595:Amino Acid Sequence; D000818:Animals; D018999:Charybdotoxin / Q000737:chemistry / Q000235:genetics; D004220:Disulfides / Q000737:chemistry; D004563:Electrochemistry; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D015221:Potassium Channels / Q000187:drug effects; D017433:Protein Structure, Secondary; D012604:Scorpion Venoms / Q000737:chemistry* / Q000235:genetics / Q000633:toxicity; D012605:Scorpions; D017386:Sequence Homology, Amino Acid; D013816:Thermodynamics
D004220:Disulfides; D015221:Potassium Channels; D012604:Scorpion Venoms; C072276:kaliotoxin; D018999:Charybdotoxin; C052567:noxiustoxin