High resolution structure of human CD59High resolution structure of human CD59

Structural highlights

2ux2 is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.8Å
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.

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

CD59 is a membrane-bound glycoprotein that protects host cells from lysis by inhibiting the terminal pathway of complement, preventing the formation and insertion of the membrane attack complex (MAC). Crystals of bacterially expressed and nonglycosylated recombinant soluble human CD59 have been obtained from three crystallization conditions, each of which gave rise to a distinct crystal form. Each crystal form led to a crystal structure at high resolution (1.15, 1.35 and 1.8 A). In one of these structures the electron-density map shows an as yet unidentified small molecule in the predicted C8/C9-binding site. The presence/absence of this ligand is linked to alternate conformations of the amino acids implicated in C8/C9 binding.

High-resolution structures of bacterially expressed soluble human CD59.,Leath KJ, Johnson S, Roversi P, Hughes TR, Smith RA, Mackenzie L, Morgan BP, Lea SM Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007 Aug 1;63(Pt, 8):648-52. Epub 2007 Jul 28. PMID:17671359[2]

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

See Also

References

  1. 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
  2. Leath KJ, Johnson S, Roversi P, Hughes TR, Smith RA, Mackenzie L, Morgan BP, Lea SM. High-resolution structures of bacterially expressed soluble human CD59. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007 Aug 1;63(Pt, 8):648-52. Epub 2007 Jul 28. PMID:17671359 doi:10.1107/S1744309107033477

2ux2, resolution 1.80Å

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