View source for 1h0j


==Structural Basis of the Membrane-induced Cardiotoxin A3 Oligomerization==
<StructureSection load='1h0j' size='340' side='right'caption='[[1h0j]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1h0j]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Naja_atra Naja atra]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H0J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H0J FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SDS:DODECYL+SULFATE'>SDS</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1h0j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h0j OCA], [https://pdbe.org/1h0j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h0j RCSB], [https://www.ebi.ac.uk/pdbsum/1h0j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h0j ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/3SA3_NAJAT 3SA3_NAJAT] Basic protein that binds to cell membrane and depolarizes cardiomyocytes. This cytotoxin also possesses lytic activity on many other cells, including red blood cells (PubMed:8182052). Interaction with sulfatides in the cell membrane induces pore formation and cell internalization. Cytotoxicity is due to pore formation, and to another mechanism independent of membrane-damaging activity. When internalized, it targets the mitochondrial membrane and induces mitochondrial swelling and fragmentation. It inhibits protein kinases C. It binds to the integrin alpha-V/beta-3 (ITGAV/ITGB3) with a moderate affinity (PubMed:16407244). It also binds with high affinity to heparin (PubMed:17685633).<ref>PMID:15922335</ref> <ref>PMID:16263708</ref> <ref>PMID:16407244</ref> <ref>PMID:17714752</ref> <ref>PMID:8182052</ref> <ref>PMID:8448165</ref> <ref>PMID:9245415</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h0/1h0j_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1h0j ConSurf].
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== Publication Abstract from PubMed ==
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.

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<ref>PMID:12660250</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Cardiotoxin 3D structures|Cardiotoxin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Naja atra]]
[[Category: Chien K-Y]]
[[Category: Forouhar F]]
[[Category: Hsiao C-D]]
[[Category: Huang W-N]]
[[Category: Liu J-H]]
[[Category: Wu W-G]]