2gx1
From Proteopedia
(New page: 200px<br /><applet load="2gx1" size="450" color="white" frame="true" align="right" spinBox="true" caption="2gx1" /> '''Solution structure and alanine scan of a spi...) |
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'''Solution structure and alanine scan of a spider toxin that affects the activation of mammalian sodium channels'''<br /> | '''Solution structure and alanine scan of a spider toxin that affects the activation of mammalian sodium channels'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Magi 5, from the hexathelid spider Macrothele gigas, is a 29-residue | + | Magi 5, from the hexathelid spider Macrothele gigas, is a 29-residue polypeptide containing three disulfide bridges. It binds specifically to receptor site 4 on mammalian voltage-gated sodium channels and competes with scorpion beta-toxins, such as Css IV from Centruroides suffusus suffusus. As a consequence, Magi 5 shifts the activation voltage of the mammalian rNav1.2a channel to more hyperpolarized voltages, whereas the insect channel, DmNav1, is not affected. To gain insight into toxin-channel interactions, Magi 5 and 23 analogues were synthesized. The three-dimensional structure of Magi 5 in aqueous solution was determined, and its voltage-gated sodium channel-binding surfaces were mapped onto this structure using data from electrophysiological measurements on a series of Ala-substituted analogues. The structure clearly resembles the inhibitor cystine knot structural motif, although the triple-stranded beta-sheet typically found in that motif is partially distorted in Magi 5. The interactive surface of Magi 5 toward voltage-gated sodium channels resembles in some respects the Janus-faced atracotoxins, with functionally important charged residues on one face of the toxin and hydrophobic residues on the other. Magi 5 also resembles the scorpion beta-toxin Css IV, which has distinct nonpolar and charged surfaces that are critical for channel binding and has a key Glu involved in voltage sensor trapping. These two distinct classes of toxin, with different amino acid sequences and different structures, may utilize similar groups of residues on their surface to achieve the common end of modifying voltage-gated sodium channel function. |
==About this Structure== | ==About this Structure== | ||
| - | 2GX1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http:// | + | 2GX1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GX1 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Bosmans, F.]] | [[Category: Bosmans, F.]] | ||
[[Category: Corzo, G.]] | [[Category: Corzo, G.]] | ||
| - | [[Category: Norton, R | + | [[Category: Norton, R S.]] |
| - | [[Category: Sabo, J | + | [[Category: Sabo, J K.]] |
[[Category: Tytgat, J.]] | [[Category: Tytgat, J.]] | ||
[[Category: Villegas, E.]] | [[Category: Villegas, E.]] | ||
[[Category: spider toxin]] | [[Category: spider toxin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:36:17 2008'' |
Revision as of 15:36, 21 February 2008
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Solution structure and alanine scan of a spider toxin that affects the activation of mammalian sodium channels
Overview
Magi 5, from the hexathelid spider Macrothele gigas, is a 29-residue polypeptide containing three disulfide bridges. It binds specifically to receptor site 4 on mammalian voltage-gated sodium channels and competes with scorpion beta-toxins, such as Css IV from Centruroides suffusus suffusus. As a consequence, Magi 5 shifts the activation voltage of the mammalian rNav1.2a channel to more hyperpolarized voltages, whereas the insect channel, DmNav1, is not affected. To gain insight into toxin-channel interactions, Magi 5 and 23 analogues were synthesized. The three-dimensional structure of Magi 5 in aqueous solution was determined, and its voltage-gated sodium channel-binding surfaces were mapped onto this structure using data from electrophysiological measurements on a series of Ala-substituted analogues. The structure clearly resembles the inhibitor cystine knot structural motif, although the triple-stranded beta-sheet typically found in that motif is partially distorted in Magi 5. The interactive surface of Magi 5 toward voltage-gated sodium channels resembles in some respects the Janus-faced atracotoxins, with functionally important charged residues on one face of the toxin and hydrophobic residues on the other. Magi 5 also resembles the scorpion beta-toxin Css IV, which has distinct nonpolar and charged surfaces that are critical for channel binding and has a key Glu involved in voltage sensor trapping. These two distinct classes of toxin, with different amino acid sequences and different structures, may utilize similar groups of residues on their surface to achieve the common end of modifying voltage-gated sodium channel function.
About this Structure
2GX1 is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
Reference
Solution structure and alanine scan of a spider toxin that affects the activation of mammalian voltage-gated sodium channels., Corzo G, Sabo JK, Bosmans F, Billen B, Villegas E, Tytgat J, Norton RS, J Biol Chem. 2007 Feb 16;282(7):4643-52. Epub 2006 Dec 5. PMID:17148449
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