1tzq: Difference between revisions
New page: left|200px<br /><applet load="1tzq" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tzq, resolution 2.3Å" /> '''Crystal structure of ... |
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== | ==Crystal structure of the equinatoxin II 8-69 double cysteine mutant== | ||
Actinoporins are eukaryotic pore-forming proteins that create 2-nm pores | <StructureSection load='1tzq' size='340' side='right'caption='[[1tzq]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1tzq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Actinia_equina Actinia equina]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TZQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TZQ 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]] 2.3Å</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=1tzq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tzq OCA], [https://pdbe.org/1tzq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tzq RCSB], [https://www.ebi.ac.uk/pdbsum/1tzq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tzq ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ACTP2_ACTEQ ACTP2_ACTEQ] Pore-forming protein that forms cations-selective hydrophilic pores of around 1 nm and causes cardiac stimulation and hemolysis. Pore formation is a multi-step process that involves specific recognition of membrane sphingomyelin (but neither cholesterol nor phosphatidylcholine) using aromatic rich region and adjacent phosphocholine (POC) binding site, firm binding to the membrane (mainly driven by hydrophobic interactions) accompanied by the transfer of the N-terminal region to the lipid-water interface and finally pore formation after oligomerization of several monomers. Cytolytic effects include red blood cells hemolysis, platelet aggregation and lysis, cytotoxic and cytostatic effects on fibroblasts. Lethality in mammals has been ascribed to severe vasospasm of coronary vessels, cardiac arrhythmia, and inotropic effects. | |||
== 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/tz/1tzq_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=1tzq ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Actinoporins are eukaryotic pore-forming proteins that create 2-nm pores in natural and model lipid membranes by the self-association of four monomers. The regions that undergo conformational change and form part of the transmembrane pore are currently being defined. It was shown recently that the N-terminal region (residues 10-28) of equinatoxin, an actinoporin from Actinia equina, participates in building of the final pore wall. Assuming that the pore is formed solely by a polypeptide chain, other parts of the toxin should constitute the conductive channel and here we searched for these regions by disulfide scanning mutagenesis. Only double cysteine mutants where the N-terminal segment 1-30 was attached to the beta-sandwich exhibited reduced hemolytic activity upon disulfide formation, showing that other parts of equinatoxin, particularly the beta-sandwich and importantly the C-terminal alpha-helix, do not undergo large conformational rearrangements during the pore formation. The role of the beta-sandwich stability was independently assessed via destabilization of a part of its hydrophobic core by mutations of the buried Trp117. These mutants were considerably less stable than the wild-type but exhibited similar or slightly lower permeabilizing activity. Collectively these results show that a flexible N-terminal region and stable beta-sandwich are pre-requisite for proper pore formation by the actinoporin family. | |||
Pore formation by equinatoxin, a eukaryotic pore-forming toxin, requires a flexible N-terminal region and a stable beta-sandwich.,Kristan K, Podlesek Z, Hojnik V, Gutierrez-Aguirre I, Guncar G, Turk D, Gonzalez-Manas JM, Lakey JH, Macek P, Anderluh G J Biol Chem. 2004 Nov 5;279(45):46509-17. Epub 2004 Aug 20. PMID:15322132<ref>PMID:15322132</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1tzq" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Cytolysin 3D structures|Cytolysin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Actinia equina]] | [[Category: Actinia equina]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Anderluh | [[Category: Anderluh G]] | ||
[[Category: Gonzalez-Maas | [[Category: Gonzalez-Maas JM]] | ||
[[Category: Guncar | [[Category: Guncar G]] | ||
[[Category: Gutirrez-Aguirre | [[Category: Gutirrez-Aguirre I]] | ||
[[Category: Hojnik | [[Category: Hojnik V]] | ||
[[Category: Kristan | [[Category: Kristan K]] | ||
[[Category: Lakey | [[Category: Lakey JH]] | ||
[[Category: Podlesek | [[Category: Podlesek Z]] | ||
[[Category: Turk | [[Category: Turk DA]] | ||
