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| | ==Staphylococcal alpha-hemolysin H35A mutant monomer== | | ==Staphylococcal alpha-hemolysin H35A mutant monomer== |
| - | <StructureSection load='4yhd' size='340' side='right' caption='[[4yhd]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='4yhd' size='340' side='right'caption='[[4yhd]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4yhd]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YHD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YHD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4yhd]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YHD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YHD FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.801Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hly, hla ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4yhd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yhd OCA], [http://pdbe.org/4yhd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yhd RCSB], [http://www.ebi.ac.uk/pdbsum/4yhd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yhd ProSAT]</span></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=4yhd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yhd OCA], [https://pdbe.org/4yhd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yhd RCSB], [https://www.ebi.ac.uk/pdbsum/4yhd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yhd ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HLA_STAAU HLA_STAAU]] Alpha-toxin binds to the membrane of eukaryotic cells resulting in the release of low-molecular weight molecules and leading to an eventual osmotic lysis. Heptamer oligomerization and pore formation is required for lytic activity. | + | [https://www.uniprot.org/uniprot/HLA_STAAU HLA_STAAU] Alpha-toxin binds to the membrane of eukaryotic cells resulting in the release of low-molecular weight molecules and leading to an eventual osmotic lysis. Heptamer oligomerization and pore formation is required for lytic activity. |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Staphylococcal alpha-hemolysin (alpha-HL) is a beta-barrel pore-forming toxin (PFT) expressed by Staphylococcus aureus. alpha-HL is secreted as a water-soluble monomeric protein, which binds to target membranes and forms membrane-inserted heptameric pores. To explore the pore-forming mechanism of alpha-HL in detail, we determined the crystal structure of the alpha-HL monomer and prepore using H35A mutant and W179A/R200A mutant, respectively. Although the overall structure of the monomer was similar to that of other staphylococcal PFTs, a marked difference was observed in the N-terminal amino latch, which bent toward the prestem. Moreover, the prestem was fastened by the cap domain with a key hydrogen bond between Asp45 and Tyr118. Prepore structure showed that the transmembrane region is roughly formed with flexibility, although the upper half of the beta-barrel is formed appropriately. Structure comparison among monomer, prepore and pore revealed a series of motions, in which the N-terminal amino latch released upon oligomerization destroys its own key hydrogen bond betweem Asp45-Try118. This action initiated the protrusion of the prestem. Y118F mutant and the N-terminal truncated mutant markedly decreased in the hemolytic activity, indicating the importance of the key hydrogen bond and the N-terminal amino latch on the pore formation. Based on these observations, we proposed a dynamic molecular mechanism of pore formation for alpha-HL.
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| - | Structural basis for pore-forming mechanism of staphylococcal alpha-hemolysin.,Sugawara T, Yamashita D, Kato K, Peng Z, Ueda J, Kaneko J, Kamio Y, Tanaka Y, Yao M Toxicon. 2015 Sep 28. pii: S0041-0101(15)30093-3. doi:, 10.1016/j.toxicon.2015.09.033. PMID:26428390<ref>PMID:26428390</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 4yhd" style="background-color:#fffaf0;"></div>
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| | ==See Also== | | ==See Also== |
| - | *[[Hemolysin|Hemolysin]] | + | *[[Hemolysin 3D structures|Hemolysin 3D structures]] |
| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Kato, K]] | + | [[Category: Large Structures]] |
| - | [[Category: Sugawara, T]] | + | [[Category: Staphylococcus aureus]] |
| - | [[Category: Tanaka, Y]] | + | [[Category: Kato K]] |
| - | [[Category: Yao, M]] | + | [[Category: Sugawara T]] |
| - | [[Category: Immunoglobulin like fold]] | + | [[Category: Tanaka Y]] |
| - | [[Category: Monomer]] | + | [[Category: Yao M]] |
| - | [[Category: Toxin]]
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