Conservation in decay accelerating factor (DAF) structure among primates.
The decay accelerating factor (DAF, CD55) protects self cells from activation of autologous complement on their surfaces. It functions to disable the C3 convertases, the central amplification enzymes of the cascade. Its active site(s) are contained within four approximately 60 amino acid long units, termed complement control protein repeats (CCPs), which are suspended above the cell surface on a 68 amino acid long serine/threonine (S/T)-rich cushion that derives from three exons. We previously proposed a molecular model of human DAF's four CCPs in which certain amino acids were postulated to be recognition sites for the interaction between DAF and the C3 convertases. In the current study, we characterized DAF in five non-human primates: the great apes, gorilla and common chimpanzee, and the Old World monkeys: hamadryas baboon, Rhesus macaque, and patas monkey. Amino acid homology to human DAF was approximately 98% for the two great apes and 83% for the three Old World monkeys. The above cited putative ligand interactive residues were found to be fully conserved in all of the non-human primates, although there were amino acid changes outside of these areas. In the chimpanzee, alternative splicing of the S/T region was found potentially to be the source of multiple protein isoforms in erythrocytes, whereas in the patas monkey, similar alternative splicing was observed but only one protein band was seen. Interestingly, a Rhesus macaque was found to exhibit a phenomenon paralleling the human Cromer Dr(a-) blood group, in which a 44-base pair deletion in CCP3 leads to a frameshift and early STOP codon.
Kuttner-Kondo
L
L
Department of Pathology, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA.
Subramanian
V B
VB
Atkinson
J P
JP
Yu
J
J
Medof
M E
ME
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D018958:CD55 Antigens / Q000737:chemistry / Q000235:genetics*; D002460:Cell Line; D003176:Complement C3; D004901:Erythrocebus patas / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology; D017353:Gene Deletion; D014644:Genetic Variation; D006071:Gorilla gorilla / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008253:Macaca mulatta / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D002679:Pan troglodytes / Q000276:immunology; D010215:Papio / Q000276:immunology; D011323:Primates / Q000235:genetics / Q000276:immunology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D018958:CD55 Antigens; D003176:Complement C3