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2ofs

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Revision as of 17:11, 19 January 2015

Crystal structure of human CD59

Structural highlights

2ofs is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	CD59 (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Human CD59 is a small membrane-bound glycoprotein that functions as an inhibitor of the membrane-attack complex (MAC) of the complement system by binding the complement proteins C8 and C9. The crystal structure of a soluble construct of CD59 has been determined to 2.1 A resolution. When compared with previous models of CD59 determined using NMR, some interesting differences are noted, including the position of helix alpha1, which contributes to the binding surface for C8 and C9. Interestingly, the crystal structure superimposes more closely with an updated NMR model of CD59 that was produced using Monte Carlo minimization, including helix alpha1. Mapping of mutations associated with enhanced or lowered inhibitory function of CD59 show the binding region to be located in a crevice between alpha1 and a three-stranded beta-sheet, as has been identified previously. Residues in the core of this region are well ordered in the electron density, in part owing to a network of stabilizing covalent and noncovalent interactions, and manifest an interesting 'striped' distribution of hydrophobic and basic residues. Docking of the same peptide that was modeled previously into the NMR structure shows that Arg55, which has been postulated to exist in 'open' and 'closed' positions, is intermediate in position between these two and is well placed to contact the peptide. Further clues regarding how CD59 interacts with small peptides arise from the crystal packing of this structure, which shows that a symmetry-related loop comprising residues 20-24 occupies a spatially similar position to the modeled peptide. This higher resolution structure of CD59 will facilitate a more precise dissection of its interactions with C8 and C9 and thus increase the likelihood of designing enhanced CD59-based therapeutics.

Crystal structure of CD59: implications for molecular recognition of the complement proteins C8 and C9 in the membrane-attack complex.,Huang Y, Fedarovich A, Tomlinson S, Davies C Acta Crystallogr D Biol Crystallogr. 2007 Jun;63(Pt 6):714-21. Epub 2007, May 15. PMID:17505110^[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
↑ Huang Y, Fedarovich A, Tomlinson S, Davies C. Crystal structure of CD59: implications for molecular recognition of the complement proteins C8 and C9 in the membrane-attack complex. Acta Crystallogr D Biol Crystallogr. 2007 Jun;63(Pt 6):714-21. Epub 2007, May 15. PMID:17505110 doi:10.1107/S0907444907015557

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2ofs"

Categories: Homo sapiens | Davies, C | Complement inhibitor | Signaling protein

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2ofs]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OFS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2OFS FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CD59 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CD59 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ofs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ofs OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ofs RCSB], [http://www.ebi.ac.uk/pdbsum/2ofs PDBsum]</span></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=2ofs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ofs OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ofs RCSB], [http://www.ebi.ac.uk/pdbsum/2ofs PDBsum]</span></td></tr>
-<table>
+</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>
@@ Line 36: / Line 36: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Davies, C.]]
+[[Category: Davies, C]]
 [[Category: Complement inhibitor]]
 [[Category: Signaling protein]]

2ofs

From Proteopedia

Revision as of 17:11, 19 January 2015

Crystal structure of human CD59

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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