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[[Image:7AHL-snapshot-800x800-31278.png|right|220px]] '''&#945;-Hemolysin''' from ''Staphlococcus aureus'' is a [http://en.wikipedia.org/wiki/Pore-forming_toxin pore-forming toxin] made of seven repeats of an identical monomer arranged in a ring. The structural basis of the toxic activity was readily revealed when the structure of the ring was solved. ===ALPHA-HEMOLYSIN FROM STAPHYLOCOCCUS AUREUS=== <!-- The line below this paragraph, {{ABSTRACT_PUBMED_8943190}}, adds the Publication Abstract to the page (as it appears on PubMed at http://www.pubmed.gov), where 8943190 is the PubMed ID number. --> {{ABSTRACT_PUBMED_8943190}} ==Background== <!--Hoping to get David Briggs to work on this--> ''Staphylococcus aureus'' is often pathogenic to humans and relies on several virulence factors in the course of the infections. &#945;-hemolysin is one such virulencce factor that forms pores in target cells<ref>PMID:12972152</ref>, similar to other [[Hemolysin|hemolsyins]]. ==About this Structure== <table width=401' align='right' cellpadding='0'><tr><td rowspan='2'>&nbsp;</td><td bgcolor='#eeeeee'> <StructureSection load='7ahl' size='400' side='right' scene='7ahl/Davebriggscolor/4' pspeed='7' caption='Hemolysin ([[7ahl]]), resolution 1.89&Aring;. '> ====The &#945;-hemolysin oligomer==== &#945;-hemolysin ([[7ahl]]) is <scene name='40/404876/Davebriggscolor/1'>a 7 chain structure of protein sequences</scene> from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Each chain in the oligomeric complex is <scene name='7ahl/Monomer/2'>an identical monomer</scene>; the other monomers are translucent to emphasize one of the seven monomers. Note the seven-fold rotational symmetry. {{Link Toggle FancyCartoonHighQualityView}}. Seven monomers come together in a ring, with <scene name='7ahl/Stalk/2'>each monomer donating 2 β-hairpins to form the stalk that protrudes from the bottom of the structure</scene>. {{Link Toggle FancyCartoonHighQualityView}}. &nbsp; ====&#945;-hemolysin interaction with the membrane==== <scene name='Luciferase/Stalkmeasure/1'> At around 2.8 nm in height</scene>, &#945;-hemolysin's stalk is perfectly designed to span the plasma membrane of eukaryotic cells (ca. 2.5 nm or 25 &Aring;). Unlike the polar surface of more typical proteins, <scene name='7ahl/Stalkhydrophobic/1'>the stalk is hydrophobic</scene>, and is instead lipophilic or preferring to be in a lipid environment. <scene name='7ahl/Stalkhydrophobic/2'>Contrast the hydrophobic stalk with the rest of the structure</scene> which is largely polar since it would sit outside the cell.<br> KEY: {{Template:ColorKey_Polar}} {{Template:ColorKey_Hydrophobic}} <!-- Note that <scene name='7ahl/7ahlopm/2a'> used to be the best OPM scene but finally seems Jmol straightened out and I could remake scene here by copying state script from that scene in page since couldn't get in scene authoring tools. Remade better. See <scene name='40/404876/Opm_withcyl/3' But later remade again with current OPM structure and Angel's membrane-as-cylinder idea so that is why another one used in scene below --> To help give a better idea of how &#945;-hemolysin interacts with the membrane lipid bilayer, <scene name='40/404876/Current_7ahl_opm_with_cyl/5'>a slab representative of the hydrophobic core of the lipid bilayer</scene> as calculated by the [http://opm.phar.umich.edu/protein.php?pdbid=7ahl Orientations of Proteins in Membranes database](University of Michigan, USA) is shown as a cylinder with the red patch indicating the boundary closet to the outside of the cell and the blue patch indicating the boundary closest to the inside of the cell. &nbsp; &nbsp; ====The &#945;-hemolysin pore==== Displaying the surface illustrates clearly that there is <scene name='Luciferase/7ahlsurface/2'>a tunnel down the middle of the heptamer that leads to the formation of pores in the cell membrane</scene>, which is the structural basis for why these are toxins. Such pores are expectedly detrimental to the cell, allowing exodus of critical molecules, destroying the established membrane potential and ionic gradients, and contributing to osmotic swelling. {{Link Toggle FancyCartoonHighQualityView}}. </StructureSection> </td></tr><tr><td ALIGN=RIGHT bgcolor='#ffffff'> <scene name='40/404876/Davebriggscolor/1'>Initial scene</scene> &nbsp; &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; &nbsp; &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; &nbsp; &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; &nbsp; &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; &nbsp;&nbsp;&nbsp;&nbsp;&nbsp; &nbsp; &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </td></tr></table> ==Use of &#945;-hemolysin in DNA sequencing technology== In 1996, researchers from Harvard University and the University of California at Santa Cruz, including Daniel Branton, [http://www.nanoporetech.com/about-us/team/technology-advisory-board/view/17/professor-david-deamer David Deamer] and John Kasianowicz showed that the pore structure formed by &#945;-hemolysin could be used to pass a single strand of DNA through a nanopore <ref>PMID: 8943010</ref>. This was later linked to an exonuclease and a detection mechanism for residency of individual nucleotides in the base of pore to ultimately form the basis of sequencing technology finally offered by Oxford Nanopore, although the specifics of the current generation of the technology may be different <ref>Nanopore sequencing: Towards the 15-minute genome. The Economist. Technology Quarterly: Q1 2011. Mar 10th 2011. http://www.economist.com/node/18304268</ref><ref>PMID: 22556226</ref>. ==PDB entry== [[7ahl]] is a 7 chain structure of sequences from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AHL OCA]. ==Reference for the structure== <ref group="xtra">PMID:8943190</ref><references group="xtra"/> ==Notes and Literature References== {{Reflist}} ==3D structures of hemolysin== see, [[Hemolysin]] ==See Also== * [[Hemolysin]] * [[1lkf]],[[2lkf]] & [[3lkf]], Leukocidin F (Hlg B) from ''Staphylococcus aureus'' * [[1pvl]], the F component of Panton-Valentine leucocidin from ''Staphylococcus aureus'' * [[3fy3]] *[[Membrane proteins]] *[[Membrane Channels & Pumps]] ==Additional Literature and Resources== *For additional information, see: [[Toxins]] <br /> *[http://xtaldave.wordpress.com/2010/04/15/my-favourite-protein-structure/ David Briggs's Blog on &#945;-hemolsyin], which served as a template for the original adaptation of [[7ahl]] to this topic page. <br> *[http://en.wikipedia.org/wiki/Pore-forming_toxin Pore-forming toxin at Wikipedia]<br> *[http://www.ks.uiuc.edu/Research/hemolysin/ Page on Bacterial Toxin &#945;-Hemolysin] by Aleksei Aksimentiev and Klaus Schulten<br> [[Category: Staphylococcus aureus]] [[Category: Bayley, H.]] [[Category: Cheley, S.]] [[Category: Gouaux, J E.]] [[Category: Hobaugh, M.]] [[Category: Shustak, C.]] [[Category: Song, L.]] [[Category: Cytolytic protein]] [[Category: Hemolysin]] [[Category: Haemolysin]] [[Category: Transmembrane pore]] [[Category: Topic Page]] ''Page started with original page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 13:00:23 2009 for [[7ahl]]''

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