Functional and structural domains of the sixth component (C6) of human complement.

Nakano, Yasuko; Hashimoto, M.; Choi, Nam-Ho; Sugita, Yuji; Tobe, Takashi; Mazda, Toshio; Tomita, Motowo

doi:10.1248/cpb.39.432

Cited by 2 publications

(1 citation statement)

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“…Other investigators stressed the importance of the short consensus repeats (SCRs) for binding of C6 to C5 (24,32), as SCRs have also been shown to bind specifically to the C5b homologues C3b and C4b (33), suggesting an evolutionarily conserved mechanism. Nakano et al (32) claimed the existence of an enzymatic moiety of C6 and mapped it to the two serine-rich sequences of the complement control Factor I module 2 of C6. Any such moiety will be lost in the functionally active C6 of C6SD subjects and thus is unlikely be of importance for hemolytic activity.…”

Section: Discussionmentioning

confidence: 99%

Molecular basis of subtotal complement C6 deficiency. A carboxy-terminally truncated but functionally active C6.

Würzner

Hobart²,

Fernie³

et al. 1995

J. Clin. Invest.

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Individuals with subtotal complement C6 deficiency possess a C6 molecule that is 14% shorter than normal C6 and present in low but detectable concentrations (1-2% of the normal mean). We now show that this dysmorphic C6 is bactericidally active and lacks an epitope that was mapped to the most carboxy-terminal part of C6 using C6 cDNA fragments expressed as fusion proteins in the pUEX expression system. We thus predicted that the abnormal C6 molecule might be carboxy-terminally truncated and sought a mutation in an area -14% from the carboxy-terminal end of the coding sequence. By sequencing PCR-amplified products from this region, we found, in three individuals from two families, a mutation that might plausibly be responsible for the defect. All three have an abnormal 5' splice donor site of intron 15, which would probably prevent splicing. An in-frame stop codon is found 17 codons downstream from the intron boundary, which would lead to a truncated polypeptide 13.5% smaller than normal C6. This result was unexpected, as earlier studies mapped the C5b binding site, or a putative enzymatic region, to this part of C6. Interestingly, all three subjects were probably heterozygous for both subtotal C6 and complete C6 deficiency. (J. Clin. Invest. 1995. 95:1877-1883.) Key words: antigenic determinants complement membrane attack complex * immunologic diseases -meningococcal infections * RNA splicing

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Section: Discussionmentioning

confidence: 99%