Genomes and Genes
Gene Symbol: C8A
Description: complement C8 alpha chain
Alias: complement component C8 alpha chain, complement component 8 alpha subunit, complement component 8 subunit alpha, complement component 8, alpha polypeptide
- Rao A, Howard O, Ng S, Whitehead A, Colten H, Sodetz J. Complementary DNA and derived amino acid sequence of the alpha subunit of human complement protein C8: evidence for the existence of a separate alpha subunit messenger RNA. Biochemistry. 1987;26:3556-64 pubmed..Analysis of the carbohydrate composition indicates 1 or 2 asparagine-linked but no O-linked oligosaccharide chains, a result consistent with predictions from the amino acid sequence.(ABSTRACT TRUNCATED AT 250 WORDS) ..
- Hadders M, Bubeck D, Roversi P, Hakobyan S, Forneris F, Morgan B, et al. Assembly and regulation of the membrane attack complex based on structures of C5b6 and sC5b9. Cell Rep. 2012;1:200-7 pubmed publisher..These results provide a structural framework for understanding MAC pore formation and regulation, processes important for fighting infections and preventing complement-mediated tissue damage. ..
- Slade D, Chiswell B, Sodetz J. Functional studies of the MACPF domain of human complement protein C8alpha reveal sites for simultaneous binding of C8beta, C8gamma, and C9. Biochemistry. 2006;45:5290-6 pubmed..Such a result suggests that this segment of C8alpha and corresponding segments of the other MAC family members are independently folded domains. ..
- Hofsteenge J, Blommers M, Hess D, Furmanek A, Miroshnichenko O. The four terminal components of the complement system are C-mannosylated on multiple tryptophan residues. J Biol Chem. 1999;274:32786-94 pubmed..Since this module has been found in a large number of other proteins, the results suggest further candidates for C-mannosylation. ..
- Kojima T, Horiuchi T, Nishizaka H, Fukumori Y, Amano T, Nagasawa K, et al. Genetic basis of human complement C8 alpha-gamma deficiency. J Immunol. 1998;161:3762-6 pubmed..No mutations were detected in the C8gamma gene by our method. Our results indicate that the pathogenesis of C8alpha-gammaD might be caused by heterogeneous molecular defects in the C8alpha gene. ..
- Brickner A, Sodetz J. Functional domains of the alpha subunit of the eighth component of human complement: identification and characterization of a distinct binding site for the gamma chain. Biochemistry. 1985;24:4603-7 pubmed..It is concluded that the gamma subunit of C8 is located on the surface of membrane-bound C5b-8 and C5b-9. ..
- Wickham S, Hotze E, Farrand A, Polekhina G, Nero T, Tomlinson S, et al. Mapping the intermedilysin-human CD59 receptor interface reveals a deep correspondence with the binding site on CD59 for complement binding proteins C8alpha and C9. J Biol Chem. 2011;286:20952-62 pubmed publisher..Hence, ILY and the MAC proteins interact with common amino acids of hCD59 but lack detectable conservation in their binding sites for hCD59...
- Slade D, Lovelace L, Chruszcz M, Minor W, Lebioda L, Sodetz J. Crystal structure of the MACPF domain of human complement protein C8 alpha in complex with the C8 gamma subunit. J Mol Biol. 2008;379:331-42 pubmed publisher..Also observed is structural conservation of the MACPF signature motif Y/W-G-T/S-H-F/Y-X(6)-G-G in alphaMACPF and Plu-MACPF, and conservation of several key glycine residues known to be important for refolding and pore formation by CDCs. ..
- Chiswell B, Slade D, Sodetz J. Binding of the lipocalin C8gamma to human complement protein C8alpha is mediated by loops located at the entrance to the C8gamma ligand binding site. Biochim Biophys Acta. 2006;1764:1518-24 pubmed..Binding near the calyx entrance suggests C8alpha may restrict and possibly regulate access to the C8gamma ligand binding site. ..
- Hadders M, Beringer D, Gros P. Structure of C8alpha-MACPF reveals mechanism of membrane attack in complement immune defense. Science. 2007;317:1552-4 pubmed..The size of the MACPF domain is consistent with known C9 pore sizes. These data imply that these mammalian and bacterial cytolytic proteins share a common mechanism of membrane insertion. ..
- Stewart J, Sodetz J. Analysis of the specific association of the eighth and ninth components of human complement: identification of a direct role for the alpha subunit of C8. Biochemistry. 1985;24:4598-602 pubmed..These particular results indicate that there are two physically distinct sites on alpha that separately mediate association of alpha with beta and with C9. Furthermore, occupation of one site does not impair interaction at the other. ..
- Yang Z, Zhang L, Zhou B, Wang C, Jia J. [Detecting the DNA polymorphism of human complement component C8A by PCR-SSCP analysis]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2006;37:471-3 pubmedThe aim of this study is to establish a new method for detecting the DNA polymorphism of human complement component C8A. Based on the point mutation (C-->A) of C8A gene in exon3,The genotypes of 98 unrelated individuals from Han ..
- Muller Eberhard H. Molecular organization and function of the complement system. Annu Rev Biochem. 1988;57:321-47 pubmed
- Densen P, McRill C. Differential functional expression of the C8 subunits. Primary role of C8 beta in assembly of intact C8. J Immunol. 1988;141:2674-9 pubmed..Thus the availability of C8 beta determines the quantity of C8 produced. Further, these data suggest the possibility that the C8 structural genes may be differentially expressed despite their close genetic linkage. ..
- Michelotti G, Snider J, Sodetz J. Genomic organization of human complement protein C8 alpha and further examination of its linkage to C8 beta. Hum Genet. 1995;95:513-8 pubmed..Furthermore, they suggest that cDNA probes used earlier yielded misleading information because they encode exons that are distributed across large segments of genomic DNA. ..
- Theriault A, Boyd E, Whaley K, Sodetz J, Connor J. Regional chromosomal assignment of genes encoding the alpha and beta subunits of human complement protein C8 to 1p32. Hum Genet. 1992;88:703-4 pubmed
- Parker C, Sodetz J. Role of the human C8 subunits in complement-mediated bacterial killing: evidence that C8 gamma is not essential. Mol Immunol. 2002;39:453-8 pubmed..Furthermore, they provide the first direct evidence that C8 gamma is not required for complement-mediated killing of Gram-negative bacteria. ..
- Plumb M, Scibek J, Barber T, Dunlap R, Platteborze P, Sodetz J. Chimeric and truncated forms of human complement protein C8 alpha reveal binding sites for C8 beta and C8 gamma within the membrane attack complex/perforin region. Biochemistry. 1999;38:8478-84 pubmed..They also suggest that the N-terminal modules in C8 alpha are important for C9 binding and/or expression of C8 activity. ..
- Stavrakoudis A. A disulfide linked model of the complement protein C8gamma complexed with C8alpha indel peptide. J Mol Model. 2009;15:165-71 pubmed publisher..Average RMSD between backbone atoms of the indel peptide during the MD trajectory in comparison with the corresponding sequence of crystal structure of the C8alpha/gamma complex was found only 0.085 nm. ..
- Zhang L, Rittner C, Sodetz J, Schneider P, Kaufmann T. The eighth component of human complement: molecular basis of C8A (C81) polymorphism. Hum Genet. 1995;96:281-4 pubmed..We found that two common alleles, C8A*A and C8A*B, are characterized by the substitution of a single amino acid (Gln to Lys), which is caused by a point ..
- Plumb M, Sodetz J. An indel within the C8 alpha subunit of human complement C8 mediates intracellular binding of C8 gamma and formation of C8 alpha-gamma. Biochemistry. 2000;39:13078-83 pubmed
- Scibek J, Plumb M, Sodetz J. Binding of human complement C8 to C9: role of the N-terminal modules in the C8 alpha subunit. Biochemistry. 2002;41:14546-51 pubmed..These results indicate that both N-terminal modules in C8alpha have a role in forming the principal binding site for C9 and that binding may be dependent on a cooperative interaction between these modules and the C8alpha MACPF domain. ..
- Lockert D, Kaufman K, Chang C, Husler T, Sodetz J, Sims P. Identity of the segment of human complement C8 recognized by complement regulatory protein CD59. J Biol Chem. 1995;270:19723-8 pubmed..Our data also suggest that optimal interaction of CD59 with this segment of human C8 alpha is influenced by N-terminal flanking sequence in C8 alpha and by human C8 beta, but is unaffected by C8 gamma. ..
- Matthews N, Stark J, Harper P, Doran J, Jones D. Recurrent meningococcal infections associated with a functional deficiency of the C8 component of human complement. Clin Exp Immunol. 1980;39:53-9 pubmed
- Langeggen H, Berge K, Macor P, Fischetti F, Tedesco F, Hetland G, et al. Detection of mRNA for the terminal complement components C5, C6, C8 and C9 in human umbilical vein endothelial cells in vitro. APMIS. 2001;109:73-8 pubmed..By the use of reverse transcription (RT)-polymerase chain reaction (PCR) and Northern blot the presence of mRNA for complement factors C5, C6, C8 and C9 was demonstrated. ..
- Schreck S, Plumb M, Platteborze P, Kaufman K, Michelotti G, Letson C, et al. Expression and characterization of recombinant subunits of human complement component C8: further analysis of the function of C8 alpha and C8 gamma. J Immunol. 1998;161:311-8 pubmed
- Musingarimi P, Plumb M, Sodetz J. Interaction between the C8 alpha-gamma and C8 beta subunits of human complement C8: role of the C8 beta N-terminal thrombospondin type 1 module and membrane attack complex/perforin domain. Biochemistry. 2002;41:11255-60 pubmed..Results from activity assays suggest that residues within this segment also mediate binding and incorporation of C8 into the MAC. ..