Decay-accelerating factor explained

Complement decay-accelerating factor, also known as CD55 or DAF, is a protein that, in humans, is encoded by the CD55 gene.^[1]

DAF regulates the complement system on the cell surface. It recognizes C4b and C3b fragments that are created during activation of C4 (classical or lectin pathway) or C3 (alternative pathway). Interaction of DAF with cell-associated C4b of the classical and lectin pathways interferes with the conversion of C2 to C2b, thereby preventing formation of the C4b2a C3-convertase, and interaction of DAF with C3b of the alternative pathway interferes with the conversion of factor B to Bb by factor D, thereby preventing formation of the C3bBb C3 convertase of the alternative pathway. Thus, by limiting the amplification convertases of the complementcascade, DAF indirectly blocks the formation of the membrane attack complex.^[2]

This glycoprotein is broadly distributed among hematopoietic and non-hematopoietic cells. It is a determinant for the Cromer blood group system.

Structure

DAF is a 70 kDa membrane protein that attaches to the cell membrane via a glycophosphatidylinositol (GPI) anchor.

DAF contains four complement control protein (CCP) repeats with a single N-linked glycan positioned between CCP1 and CCP2. CCP2, CCP3, CCP4 and three consecutive lysine residues in a positively charged pocket between CCP2 and CCP3 are involved in its inhibition of the alternate complement pathway. CCP2 and CCP3 alone are involved in its inhibition of the classical pathway.^[3]

Pathology

Paroxysmal nocturnal hemoglobinuria

Because DAF is a GPI-anchored protein, its expression is reduced in persons with mutations that reduce GPI levels such as those with paroxysmal nocturnal hemoglobinuria (PNH). In PNH disorder, red blood cells with very low levels of DAF and CD59 undergo complement-mediated hemolysis. Symptoms include low red blood cell count (anemia), fatigue, and episodes of dark colored urine and other complications.^[4]

Infectious diseases

DAF is used as a receptor by some coxsackieviruses and other enteroviruses.^[5] Recombinant soluble DAF-Fc has been tested in mice as an anti-enterovirus therapy for heart damage;^[6] however, the human enterovirus that was tested binds much more strongly to human DAF than to mouse or rat DAF. Echoviruses and coxsackie B viruses that use human decay-accelerating factor (DAF) as a receptor do not bind the rodent analogues of DAF.^[7] and DAF-Fc has yet to be tested in humans.

Binding of DAF to human HIV-1 when the virons are budding from the surface of infected cells protects HIV-1 from complement mediated lysis.^{[8] [9]}

See also

• List of human clusters of differentiation
• CD59

Further reading

• Selinka HC, Wolde A, Sauter M, etal . Virus-receptor interactions of coxsackie B viruses and their putative influence on cardiotropism. . Med. Microbiol. Immunol. . 193 . 2–3 . 127–31 . 2004 . 12920584 . 10.1007/s00430-003-0193-y . 21083098 .
• Mikesch JH, Schier K, Roetger A, etal . The expression and action of decay-accelerating factor (CD55) in human malignancies and cancer therapy. . Cell. Oncol. . 28 . 5–6 . 223–32 . 2007 . 10.1155/2006/814816 . 17167176 . 4618202 . free .

External links

• • Cromer blood group system at BGMUT Blood Group Antigen Gene Mutation Database at NCBI, NIH

Notes and References

1. Medof ME, Lublin DM, Holers VM, Ayers DJ, Getty RR, Leykam JF, Atkinson JP, Tykocinski ML . Cloning and characterization of cDNAs encoding the complete sequence of decay-accelerating factor of human complement . Proc. Natl. Acad. Sci. U.S.A. . 84 . 7 . 2007–11 . April 1987 . 2436222 . 304572 . 10.1073/pnas.84.7.2007. 1987PNAS...84.2007M . free .
2. Web site: Molecular function for CD55 Gene.
3. Brodbeck WG, Kuttner-Kondo L, Mold C, Medof ME . Structure/function studies of human decay-accelerating factor . Immunology . 101 . 1 . 104–11 . Sep 2000 . 11012760 . 2327052. 10.1046/j.1365-2567.2000.00086.x.
4. Parker C, Omine M, Richards S, etal . Diagnosis and management of paroxysmal nocturnal hemoglobinuria . Blood . 106 . 12 . 3699–709 . 2005 . 16051736 . 10.1182/blood-2005-04-1717. 1895106.
5. Karnauchow TM, Tolson DL, Harrison BA, Altman E, Lublin DM, Dimock K . The HeLa cell receptor for enterovirus 70 is decay-accelerating factor (CD55) . J. Virol. . 70 . 8 . 5143–52 . August 1996 . 10.1128/JVI.70.8.5143-5152.1996 . 8764022 . 190469 .
6. Yanagawa B, Spiller OB, Choy J, Luo H, Cheung P, Zhang HM, Goodfellow IG, Evans DJ, Suarez A, Yang D, McManus BM . Coxsackievirus B3-associated myocardial pathology and viral load reduced by recombinant soluble human decay-accelerating factor in mice . Lab. Invest. . 83 . 1 . 75–85 . January 2003 . 12533688 . 10.1097/01.lab.0000049349.56211.09. free .
7. Spiller OB, Goodfellow IG, Evans DJ, Almond JW, Morgan BP . Echoviruses and coxsackie B viruses that use human decay-accelerating factor (DAF) as a receptor do not bind the rodent analogues of DAF . J. Infect. Dis. . 181 . 1 . 340–3 . January 2000 . 10608785 . 10.1086/315210 . 31672193 . free .
8. Marschang P, Sodroski J, Würzner R, Dierich MP . Decay-accelerating factor (CD55) protects human immunodeficiency virus type 1 from inactivation by human complement . Eur J Immunol . 25 . 1 . 285–90 . January 1995 . 7531147 . 10.1002/eji.1830250147 . 31079892 .
9. Guibinga GH, Friedmann T . Baculovirus GP64-pseudotyped HIV-based lentivirus vectors are stabilized against complement inactivation by codisplay of decay accelerating factor (DAF) or of a GP64-DAF fusion protein . Mol Ther . 11 . 4 . 645–51 . April 2005 . 15771967 . 10.1016/j.ymthe.2004.12.002 . free .