View source for 4hsc


==Crystal structure of a cholesterol dependent cytolysin==
<StructureSection load='4hsc' size='340' side='right'caption='[[4hsc]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4hsc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pyogenes_SSI-1 Streptococcus pyogenes SSI-1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HSC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HSC 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]] 2.1&#8491;</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=4hsc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hsc OCA], [https://pdbe.org/4hsc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hsc RCSB], [https://www.ebi.ac.uk/pdbsum/4hsc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hsc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TACY_STRPQ TACY_STRPQ] Sulfhydryl-activated toxin that causes cytolysis by forming pores in cholesterol containing host membranes. After binding to target membranes, the protein undergoes a major conformation change, leading to its insertion in the host membrane and formation of an oligomeric pore complex. Cholesterol may be required for binding to host membranes, membrane insertion and pore formation. Can be reversibly inactivated by oxidation (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cholesterol-dependent cytolysins (CDCs) are a large family of bacterial toxins that exhibit a dependence on the presence of membrane cholesterol in forming large pores in cell membranes. Significant changes in the three-dimensional structure of these toxins are necessary to convert the soluble monomeric protein into a membrane pore. We have determined the crystal structure of the archetypical member of the CDC family, streptolysin O (SLO), a virulence factor from Streptococcus pyogenes. The overall fold is similar to previously reported CDC structures, although the C-terminal domain is in a different orientation with respect to the rest of the molecule. Surprisingly, a signature stretch of CDC sequence called the undecapeptide motif, a key region involved in membrane recognition, adopts a very different structure in SLO to that of the well-characterized CDC perfringolysin O (PFO), although the sequences in this region are identical. An analysis reveals that, in PFO, there are complementary interactions between the motif and the rest of domain 4 that are lost in SLO. Molecular dynamics simulations suggest that the loss of a salt bridge in SLO and a cation-pi interaction are determining factors in the extended conformation of the motif, which in turn appears to result in a greater flexibility of the neighboring L1 loop that houses a cholesterol-sensing motif. These differences may explain the differing abilities of SLO and PFO to efficiently penetrate target cell membranes in the first step of toxin insertion into the membrane.

Structural studies of Streptococcus pyogenes streptolysin O provide insights into the early steps of membrane penetration.,Feil SC, Ascher DB, Kuiper MJ, Tweten RK, Parker MW J Mol Biol. 2014 Feb 20;426(4):785-92. doi: 10.1016/j.jmb.2013.11.020. Epub 2013 , Dec 3. PMID:24316049<ref>PMID:24316049</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4hsc" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cytolysin 3D structures|Cytolysin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptococcus pyogenes SSI-1]]
[[Category: Feil SC]]
[[Category: Parker MW]]