1h0j
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Cobra cardiotoxins (CTXs) have previously been shown to induce membrane | + | Cobra cardiotoxins (CTXs) have previously been shown to induce membrane fusion of vesicles formed by phospholipids such as cardiolipin or sphingomyelin. CTX can also form a pore in membrane bilayers containing a anionic lipid such as phosphatidylserine or phosphatidylglycerol. Herein, we show that the interaction of CTX with negatively charged lipids causes CTX dimerization, an important intermediate for the eventual oligomerization of CTX during the CTX-induced fusion and pore formation process. The structural basis of the lipid-induced oligomerization of CTX A3, a major CTX from Naja atra, is then illustrated by the crystal structure of CTX A3 in complex with SDS; SDS likely mimics anionic lipids of the membrane under micelle conditions at 1.9-A resolution. The crystal packing reveals distinct SDS-free and SDS-rich regions; in the latter two types of interconnecting CTX A3 dimers, D1 and D2, and several SDS molecules can be identified to stabilize D1 and D2 by simultaneously interacting with residues at each dimer interface. When the three CTXSDS complexes in the asymmetric unit are overlaid, the orientation of CTX A3 monomers relative to the SDS molecules in the crystal is strikingly similar to that of the toxin with respect to model membranes as determined by NMR and Fourier transform infrared methods. These results not only illustrate how lipid-induced CTX dimer formation may be transformed into oligomers either as inverted micelles of fusion intermediates or as membrane pore of anionic lipid bilayers but also underscore a potential role for SDS in x-ray diffraction study of protein-membrane interactions in the future. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Naja atra]] | [[Category: Naja atra]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Chien, K | + | [[Category: Chien, K Y.]] |
[[Category: Forouhar, F.]] | [[Category: Forouhar, F.]] | ||
| - | [[Category: Hsiao, C | + | [[Category: Hsiao, C D.]] |
| - | [[Category: Huang, W | + | [[Category: Huang, W N.]] |
| - | [[Category: Liu, J | + | [[Category: Liu, J H.]] |
| - | [[Category: Wu, W | + | [[Category: Wu, W G.]] |
[[Category: SDS]] | [[Category: SDS]] | ||
[[Category: cardiotoxin]] | [[Category: cardiotoxin]] | ||
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[[Category: venom]] | [[Category: venom]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:56:02 2008'' |
Revision as of 10:56, 21 February 2008
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STRUCTURAL BASIS OF THE MEMBRANE-INDUCED CARDIOTOXIN A3 OLIGOMERIZATION
Overview
Cobra cardiotoxins (CTXs) have previously been shown to induce membrane fusion of vesicles formed by phospholipids such as cardiolipin or sphingomyelin. CTX can also form a pore in membrane bilayers containing a anionic lipid such as phosphatidylserine or phosphatidylglycerol. Herein, we show that the interaction of CTX with negatively charged lipids causes CTX dimerization, an important intermediate for the eventual oligomerization of CTX during the CTX-induced fusion and pore formation process. The structural basis of the lipid-induced oligomerization of CTX A3, a major CTX from Naja atra, is then illustrated by the crystal structure of CTX A3 in complex with SDS; SDS likely mimics anionic lipids of the membrane under micelle conditions at 1.9-A resolution. The crystal packing reveals distinct SDS-free and SDS-rich regions; in the latter two types of interconnecting CTX A3 dimers, D1 and D2, and several SDS molecules can be identified to stabilize D1 and D2 by simultaneously interacting with residues at each dimer interface. When the three CTXSDS complexes in the asymmetric unit are overlaid, the orientation of CTX A3 monomers relative to the SDS molecules in the crystal is strikingly similar to that of the toxin with respect to model membranes as determined by NMR and Fourier transform infrared methods. These results not only illustrate how lipid-induced CTX dimer formation may be transformed into oligomers either as inverted micelles of fusion intermediates or as membrane pore of anionic lipid bilayers but also underscore a potential role for SDS in x-ray diffraction study of protein-membrane interactions in the future.
About this Structure
1H0J is a Single protein structure of sequence from Naja atra with as ligand. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Structural basis of membrane-induced cardiotoxin A3 oligomerization., Forouhar F, Huang WN, Liu JH, Chien KY, Wu WG, Hsiao CD, J Biol Chem. 2003 Jun 13;278(24):21980-8. Epub 2003 Mar 26. PMID:12660250
Page seeded by OCA on Thu Feb 21 12:56:02 2008
Categories: Naja atra | Single protein | Chien, K Y. | Forouhar, F. | Hsiao, C D. | Huang, W N. | Liu, J H. | Wu, W G. | SDS | Cardiotoxin | Cytotoxin | Sodium dodecyl sulfate | Venom
