5imt

From Proteopedia

(Difference between revisions)

Revision as of 06:51, 10 September 2016

Toxin receptor complex

Structural highlights

5imt is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Motoyama N, Okada N, Yamashina M, Okada H. Paroxysmal nocturnal hemoglobinuria due to hereditary nucleotide deletion in the HRF20 (CD59) gene. Eur J Immunol. 1992 Oct;22(10):2669-73. PMID:1382994 doi:http://dx.doi.org/10.1002/eji.1830221029
↑ Lawrence SL, Gorman MA, Feil SC, Mulhern TD, Kuiper MJ, Ratner AJ, Tweten RK, Morton CJ, Parker MW. Structural Basis for Receptor Recognition by the Human CD59-Responsive Cholesterol-Dependent Cytolysins. Structure. 2016 Sep 6;24(9):1488-1498. doi: 10.1016/j.str.2016.06.017. Epub 2016 , Aug 4. PMID:27499440 doi:http://dx.doi.org/10.1016/j.str.2016.06.017

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5imt"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5imt is ON HOLD  until Paper Publication
+==Toxin receptor complex==
+<StructureSection load='5imt' size='340' side='right' caption='[[5imt]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5imt]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IMT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IMT FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5imt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5imt OCA], [http://pdbe.org/5imt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5imt RCSB], [http://www.ebi.ac.uk/pdbsum/5imt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5imt 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.
-Authors:
+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>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5imt" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Feil, S C]]
+[[Category: Lawrence, S L]]
+[[Category: Morton, C J]]
+[[Category: Parker, M W]]
+[[Category: Cytolysin]]
+[[Category: Toxin]]

5imt

From Proteopedia

Revision as of 06:51, 10 September 2016

Toxin receptor complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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