| Autor: |
R H, McLean, G, Niblack, B, Julian, T, Wang, R, Wyatt, J A, Phillips, T S, Collins, J, Winkelstein, D, Valle |
| Rok vydání: |
1994 |
| Předmět: |
|
| Zdroj: |
The Journal of biological chemistry. 269(44) |
| ISSN: |
0021-9258 |
| Popis: |
The fourth component of complement (C4) is encoded by two highly homologous genes, C4A and C4B. Only one hemolytically inactive C4A allotype (C4A6) has been reported. No hemolytically inactive C4B allotype has been described. We report the first hemolytically inactive (hi) allotype of C4B, C4B*1 (hi). This unique variant was first recognized by hemolytic overlay assays and confirmed to segregate in the affected pedigree with the major histocompatibility complex haplotype A28,B35,CW4,DR6, C4A3,C4B1(hi), BFF,C2C. By single strand conformational polymorphism, we detected only a migration variant in exon 12 caused by a C to T transition in the second base of codon 459. This mutation results in a leucine substitution for proline (P459L) 1 residue downstream of a residue known to contribute to the C5-binding site. Allele-specific oligonucleotide analysis of samples demonstrated cosegregation of the mutation with the hemolytically inactive allotype in the affected pedigree. Site-directed mutagenesis and expression studies showed that the P459L mutation causes loss of hemolytic function. C4B*1(hi) is the first example of a circulating C4B protein lacking detectable hemolytic activity and the P459L mutation expands our knowledge of the C5-binding site of C4. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
