5imy: Difference between revisions
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==Trapped Toxin== | |||
<StructureSection load='5imy' size='340' side='right' caption='[[5imy]], [[Resolution|resolution]] 2.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5imy]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IMY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IMY FirstGlance]. <br> | |||
</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=5imy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5imy OCA], [http://pdbe.org/5imy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5imy RCSB], [http://www.ebi.ac.uk/pdbsum/5imy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5imy ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/CD59_HUMAN CD59_HUMAN]] Defects in CD59 are the cause of CD59 deficiency (CD59D) [MIM:[http://omim.org/entry/612300 612300]].<ref>PMID:1382994</ref> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/CD59_HUMAN CD59_HUMAN]] Potent inhibitor of the complement membrane attack complex (MAC) action. Acts by binding to the C8 and/or C9 complements of the assembling MAC, thereby preventing incorporation of the multiple copies of C9 required for complete formation of the osmolytic pore. This inhibitor appears to be species-specific. Involved in signal transduction for T-cell activation complexed to a protein tyrosine kinase. The soluble form from urine retains its specific complement binding activity, but exhibits greatly reduced ability to inhibit MAC assembly on cell membranes. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Cholesterol-dependent cytolysins (CDCs) are a family of pore-forming toxins that punch holes in the outer membrane of eukaryotic cells. Cholesterol serves as the receptor, but a subclass of CDCs first binds to human CD59. Here we describe the crystal structures of vaginolysin and intermedilysin complexed to CD59. These studies, together with small-angle X-ray scattering, reveal that CD59 binds to each at different, though overlapping, sites, consistent with molecular dynamics simulations and binding studies. The CDC consensus undecapeptide motif, which for the CD59-responsive CDCs has a proline instead of a tryptophan in the motif, adopts a strikingly different conformation between the structures; our data suggest that the proline acts as a selectivity switch to ensure CD59-dependent CDCs bind their protein receptor first in preference to cholesterol. The structural data suggest a detailed model of how these water-soluble toxins assemble as prepores on the cell surface. | |||
Structural Basis for Receptor Recognition by the Human CD59-Responsive Cholesterol-Dependent Cytolysins.,Lawrence SL, Gorman MA, Feil SC, Mulhern TD, Kuiper MJ, Ratner AJ, Tweten RK, Morton CJ, Parker MW Structure. 2016 Sep 6;24(9):1488-1498. doi: 10.1016/j.str.2016.06.017. Epub 2016 , Aug 4. PMID:27499440<ref>PMID:27499440</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5imy" style="background-color:#fffaf0;"></div> | ||
[[Category: Parker, M | == References == | ||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Lawrence, S L]] | |||
[[Category: Morton, C J]] | |||
[[Category: Parker, M W]] | |||
[[Category: Toxin-toxin receptor complex]] | |||
Revision as of 09:52, 10 September 2016
Trapped ToxinTrapped Toxin
Structural highlights
Disease[CD59_HUMAN] Defects in CD59 are the cause of CD59 deficiency (CD59D) [MIM:612300].[1] Function[CD59_HUMAN] Potent inhibitor of the complement membrane attack complex (MAC) action. Acts by binding to the C8 and/or C9 complements of the assembling MAC, thereby preventing incorporation of the multiple copies of C9 required for complete formation of the osmolytic pore. This inhibitor appears to be species-specific. Involved in signal transduction for T-cell activation complexed to a protein tyrosine kinase. The soluble form from urine retains its specific complement binding activity, but exhibits greatly reduced ability to inhibit MAC assembly on cell membranes. Publication Abstract from PubMedCholesterol-dependent cytolysins (CDCs) are a family of pore-forming toxins that punch holes in the outer membrane of eukaryotic cells. Cholesterol serves as the receptor, but a subclass of CDCs first binds to human CD59. Here we describe the crystal structures of vaginolysin and intermedilysin complexed to CD59. These studies, together with small-angle X-ray scattering, reveal that CD59 binds to each at different, though overlapping, sites, consistent with molecular dynamics simulations and binding studies. The CDC consensus undecapeptide motif, which for the CD59-responsive CDCs has a proline instead of a tryptophan in the motif, adopts a strikingly different conformation between the structures; our data suggest that the proline acts as a selectivity switch to ensure CD59-dependent CDCs bind their protein receptor first in preference to cholesterol. The structural data suggest a detailed model of how these water-soluble toxins assemble as prepores on the cell surface. Structural Basis for Receptor Recognition by the Human CD59-Responsive Cholesterol-Dependent Cytolysins.,Lawrence SL, Gorman MA, Feil SC, Mulhern TD, Kuiper MJ, Ratner AJ, Tweten RK, Morton CJ, Parker MW Structure. 2016 Sep 6;24(9):1488-1498. doi: 10.1016/j.str.2016.06.017. Epub 2016 , Aug 4. PMID:27499440[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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