1seg
From Proteopedia
(New page: 200px<br /><applet load="1seg" size="450" color="white" frame="true" align="right" spinBox="true" caption="1seg, resolution 1.30Å" /> '''Crystal structure of...) |
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'''Crystal structure of a toxin chimera between Lqh-alpha-IT from the scorpion Leiurus quinquestriatus hebraeus and AAH2 from Androctonus australis hector'''<br /> | '''Crystal structure of a toxin chimera between Lqh-alpha-IT from the scorpion Leiurus quinquestriatus hebraeus and AAH2 from Androctonus australis hector'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Scorpion alpha-toxins are similar in their mode of action and | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1SEG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Androctonus_australis_hector Androctonus australis hector] with SO4, NO3 and PPI as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1SEG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Androctonus_australis_hector Androctonus australis hector] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=NO3:'>NO3</scene> and <scene name='pdbligand=PPI:'>PPI</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SEG OCA]. |
==Reference== | ==Reference== | ||
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[[Category: toxin]] | [[Category: toxin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:00:39 2008'' |
Revision as of 13:00, 21 February 2008
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Crystal structure of a toxin chimera between Lqh-alpha-IT from the scorpion Leiurus quinquestriatus hebraeus and AAH2 from Androctonus australis hector
Overview
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.
About this Structure
1SEG is a Single protein structure of sequence from Androctonus australis hector with , and as ligands. Full crystallographic information is available from OCA.
Reference
Molecular basis of the high insecticidal potency of scorpion alpha-toxins., Karbat I, Frolow F, Froy O, Gilles N, Cohen L, Turkov M, Gordon D, Gurevitz M, J Biol Chem. 2004 Jul 23;279(30):31679-86. Epub 2004 May 8. PMID:15133045
Page seeded by OCA on Thu Feb 21 15:00:39 2008
Categories: Androctonus australis hector | Single protein | Cohen, L. | Frolow, F. | Froy, O. | Gilles, N. | Gordon, D. | Gurevitz, M. | Karbat, I. | Turkov, M. | NO3 | PPI | SO4 | Chimera | Scorpion | Toxin
