1SEG

Crystal structure of a toxin chimera between Lqh-alpha-IT from the scorpion Leiurus quinquestriatus hebraeus and AAH2 from Androctonus australis hector

1SEG の概要

• エントリーDOI: 10.2210/pdb1seg/pdb
• 関連するPDBエントリー: 1AHO 1LQH
• 分子名称: AAH2: LQH-ALPHA-IT (FACE) CHIMERIC TOXIN, SULFATE ION, NITRATE ION, ... (5 entities in total)
• 機能のキーワード: toxin, chimera, scorpion
• 由来する生物種: Androctonus australis hector
• 細胞内の位置: Secreted: P01484
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 7717.65

構造登録者

Karbat, I.,Frolow, F.,Froy, O.,Gilles, N.,Cohen, L.,Turkov, M.,Gordon, D.,Gurevitz, M. (登録日: 2004-02-17, 公開日: 2004-08-31, 最終更新日: 2024-11-13)

主引用文献

Karbat, I.,Frolow, F.,Froy, O.,Gilles, N.,Cohen, L.,Turkov, M.,Gordon, D.,Gurevitz, M.
Molecular basis of the high insecticidal potency of scorpion alpha-toxins.
J.Biol.Chem., 279:31679-31686, 2004

PubMed Abstract: Scorpion alpha-toxins are similar in their mode of action and three-dimensional structure but differ considerably in affinity for various voltage-gated sodium channels (NaChs). To clarify the molecular basis of the high potency of the alpha-toxin LqhalphaIT (from Leiurus quinquestriatus hebraeus) for insect NaChs, we identified by mutagenesis the key residues important for activity. We have found that the functional surface is composed of two distinct domains: a conserved "Core-domain" formed by residues of the loops connecting the secondary structure elements of the molecule core and a variable "NC-domain" formed by a five-residue turn (residues 8-12) and a C-terminal segment (residues 56-64). We further analyzed the role of these domains in toxin activity on insects by their stepwise construction onto the scaffold of the anti-mammalian alpha-toxin, Aah2 (from Androctonus australis hector). The chimera harboring both domains, Aah2(LqhalphaIT(face)), was as active to insects as LqhalphaIT. Structure determination of Aah2(LqhalphaIT(face)) by x-ray crystallography revealed that the NC-domain deviates from that of Aah2 and forms an extended protrusion off the molecule core as appears in LqhalphaIT. Notably, such a protrusion is observed in all alpha-toxins active on insects. Altogether, the division of the functional surface into two domains and the unique configuration of the NC-domain illuminate the molecular basis of alpha-toxin specificity for insects and suggest a putative binding mechanism to insect NaChs.

PubMed: 15133045
DOI: 10.1074/jbc.M402048200

実験手法

X-RAY DIFFRACTION (1.3 Å)