“Decay-accelerating factor”的意思、由来-开放百科全书

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 C4b2b 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 complement

cascade, 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. In that disorder, red blood cells with very low levels of DAF and CD59 undergo complement-mediated hemolysis.^[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.

See also

References

1. ^{{cite journal | vauthors = Medof ME, Lublin DM, Holers VM, Ayers DJ, Getty RR, Leykam JF, Atkinson JP, Tykocinski ML | title = Cloning and characterization of cDNAs encoding the complete sequence of decay-accelerating factor of human complement | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 84 | issue = 7 | pages = 2007–11 |date=April 1987 | pmid = 2436222 | pmc = 304572 | doi = 10.1073/pnas.84.7.2007| url = | issn = }}
2. ^{{cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=CD55#function|title=Molecular function for CD55 Gene}}
3. ^{{cite journal | vauthors = Brodbeck WG, Kuttner-Kondo L, Mold C, Medof ME | title = Structure/function studies of human decay-accelerating factor | journal = Immunology | volume = 101 | issue = 1 | pages = 104–11 |date=Sep 2000 | pmid = 11012760 | pmc = 2327052| doi = 10.1046/j.1365-2567.2000.00086.x| url = | issn = }}
4. ^{{cite journal |vauthors=Parker C, Omine M, Richards S, etal |title=Diagnosis and management of paroxysmal nocturnal hemoglobinuria |journal=Blood |volume=106 |issue=12 |pages=3699–709 |year=2005 |pmid=16051736 |doi=10.1182/blood-2005-04-1717| pmc=1895106}}
5. ^{{cite journal | vauthors = Karnauchow TM, Tolson DL, Harrison BA, Altman E, Lublin DM, Dimock K | title = The HeLa cell receptor for enterovirus 70 is decay-accelerating factor (CD55) | journal = J. Virol. | volume = 70 | issue = 8 | pages = 5143–52 |date=August 1996 | pmid = 8764022 | pmc = 190469 | doi = | url = | issn = }}
6. ^{{cite journal | vauthors = Yanagawa B, Spiller OB, Choy J, Luo H, Cheung P, Zhang HM, Goodfellow IG, Evans DJ, Suarez A, Yang D, McManus BM | title = Coxsackievirus B3-associated myocardial pathology and viral load reduced by recombinant soluble human decay-accelerating factor in mice | journal = Lab. Invest. | volume = 83 | issue = 1 | pages = 75–85 |date=January 2003 | pmid = 12533688 | doi = 10.1097/01.lab.0000049349.56211.09| url = | issn = }}
7. ^{{cite journal | vauthors = Spiller OB, Goodfellow IG, Evans DJ, Almond JW, Morgan BP | title = Echoviruses and coxsackie B viruses that use human decay-accelerating factor (DAF) as a receptor do not bind the rodent analogues of DAF | journal = J. Infect. Dis. | volume = 181 | issue = 1 | pages = 340–3 |date=January 2000 | pmid = 10608785 | doi = 10.1086/315210 | url = | issn = }}