4bik

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
{{STRUCTURE_4bik| PDB=4bik | SCENE= }}
+
==Structure of a disulfide locked mutant of Intermedilysin with human CD59==
-
===Structure of a disulfide locked mutant of Intermedilysin with human CD59===
+
<StructureSection load='4bik' size='340' side='right' caption='[[4bik]], [[Resolution|resolution]] 3.49&Aring;' scene=''>
-
{{ABSTRACT_PUBMED_23665225}}
+
== Structural highlights ==
-
 
+
<table><tr><td colspan='2'>[[4bik]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Streptococcus_intermedius Streptococcus intermedius]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BIK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BIK FirstGlance]. <br>
-
==Disease==
+
</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=4bik FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bik OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bik RCSB], [http://www.ebi.ac.uk/pdbsum/4bik PDBsum]</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>
[[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 ==
 +
Pore-forming proteins containing the structurally conserved membrane attack complex/perforin fold play an important role in immunity and host-pathogen interactions. Intermedilysin (ILY) is an archetypal member of a cholesterol-dependent cytolysin subclass that hijacks the complement receptor CD59 to make cytotoxic pores in human cells. ILY directly competes for the membrane attack complex binding site on CD59, rendering cells susceptible to complement lysis. To understand how these bacterial pores form in lipid bilayers and the role CD59 plays in complement regulation, we determined the crystal structure of human CD59 bound to ILY. Here, we show the ILY-CD59 complex at 3.5 A resolution and identify two interfaces mediating this host-pathogen interaction. An ILY-derived peptide based on the binding site inhibits pore formation in a CD59-containing liposome model system. These data provide insight into how CD59 coordinates ILY monomers, nucleating an early prepore state, and suggest a potential mechanism of inhibition for the complement terminal pathway.
-
==Function==
+
Structural Basis for Recognition of the Pore-Forming Toxin Intermedilysin by Human Complement Receptor CD59.,Johnson S, Brooks NJ, Smith RA, Lea SM, Bubeck D Cell Rep. 2013 May 30;3(5):1369-77. doi: 10.1016/j.celrep.2013.04.029. Epub 2013 , May 9. PMID:23665225<ref>PMID:23665225</ref>
-
[[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.
+
-
==About this Structure==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[4bik]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Streptococcus_intermedius Streptococcus intermedius]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BIK OCA].
+
</div>
-
==Reference==
+
==See Also==
-
<ref group="xtra">PMID:023665225</ref><references group="xtra"/><references/>
+
*[[CD59|CD59]]
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Streptococcus intermedius]]
[[Category: Streptococcus intermedius]]
-
[[Category: Brooks, N J.]]
+
[[Category: Brooks, N J]]
-
[[Category: Bubeck, D.]]
+
[[Category: Bubeck, D]]
-
[[Category: Johnson, S.]]
+
[[Category: Johnson, S]]
-
[[Category: Lea, S M.]]
+
[[Category: Lea, S M]]
-
[[Category: Smith, R A.G.]]
+
[[Category: Smith, R A.G]]
[[Category: Cholesterol dependent cytotoxin]]
[[Category: Cholesterol dependent cytotoxin]]
[[Category: Complement]]
[[Category: Complement]]
[[Category: Immune system]]
[[Category: Immune system]]
[[Category: Membrane attack complex]]
[[Category: Membrane attack complex]]

Revision as of 09:32, 21 December 2014

Structure of a disulfide locked mutant of Intermedilysin with human CD59

4bik, resolution 3.49Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools