1h0j
From Proteopedia
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==Overview== | ==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 ... | + | 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== | ||
| - | 1H0J is a | + | 1H0J is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Naja_atra Naja atra] with SDS as [http://en.wikipedia.org/wiki/ligand ligand]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1H0J OCA]. |
==Reference== | ==Reference== | ||
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[[Category: venom]] | [[Category: venom]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 13:35:09 2007'' |
Revision as of 11:29, 5 November 2007
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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 SDS as ligand. Structure known Active Site: AC1. 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 Mon Nov 5 13:35:09 2007
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
