4bik

From Proteopedia

(Difference between revisions)

Revision as of 15:05, 4 August 2016

Structure of a disulfide locked mutant of Intermedilysin with human CD59

Structural highlights

4bik is a 4 chain structure with sequence from Atcc 27335 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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

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.

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^[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
↑ Johnson S, Brooks NJ, Smith RA, Lea SM, Bubeck D. Structural Basis for Recognition of the Pore-Forming Toxin Intermedilysin by Human Complement Receptor CD59. Cell Rep. 2013 May 30;3(5):1369-77. doi: 10.1016/j.celrep.2013.04.029. Epub 2013 , May 9. PMID:23665225 doi:10.1016/j.celrep.2013.04.029

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4bik"

@@ Line 1: / Line 1: @@
 ==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=''>
 == 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>
+<table><tr><td colspan='2'>[[4bik]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_27335 Atcc 27335] and [http://en.wikipedia.org/wiki/Human Human]. 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>
-</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>
+</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://pdbe.org/4bik PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bik RCSB], [http://www.ebi.ac.uk/pdbsum/4bik PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bik ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4bik" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 24: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Atcc 27335]]
-[[Category: Streptococcus intermedius]]
+[[Category: Human]]
 [[Category: Brooks, N J]]
 [[Category: Bubeck, D]]

4bik

From Proteopedia

Revision as of 15:05, 4 August 2016

Structure of a disulfide locked mutant of Intermedilysin with human CD59

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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