Human factor H and C4b-binding protein serve as factor I-cofactors both encompassing inactivation of C3b and C4b

Seya, Tsukasa; Nakamura, Kimiyo; Masaki, Takahisa; Ichihara-Itoh, Chikako; Matsumoto, Misako; Nagasawa, Shigeharu

doi:10.1016/0161-5890(94)00157-v

Cited by 41 publications

(22 citation statements)

References 36 publications

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“…Indeed, Krych and colleagues observed that altered binding of C3b or C4b to CR1 always correlated with mutations that removed a positive charge or added a negative charge in CR1 (25). Accordingly, it has been observed that binding affinity of cofactors to C3b and C4b increases concomitantly with decrease in ionic strength of the buffer (26). Long-range electrostatic forces together with favorable charge-charge interactions could be crucial for the formation of many short-lived macromolecular complexes within the complement cascade.…”

Section: Discussionmentioning

confidence: 99%

Human C4b-Binding Protein Has Overlapping, But Not Identical, Binding Sites for C4b and Streptococcal M Proteins

Blom

Berggård

Webb

et al. 2000

The Journal of Immunology

104

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Many strains of Streptococcus pyogenes bind C4b-binding protein (C4BP), an inhibitor of complement activation. The binding is mediated by surface M proteins in a fashion that has been suggested to mimic the binding of C4b. We have previously shown that a positively charged cluster at the interface between complement control protein domains 1 and 2 of C4BP α-chain is crucial for the C4b-C4BP interaction. To extend this observation, and to investigate the interaction with M proteins, we constructed and characterized a total of nine mutants of C4BP. We identified a key recognition surface for M proteins that overlaps with the C4b binding site because substitution of R64 and H67 by Gln dramatically reduces binding to both ligands. However, the analysis of all mutants indicates that the binding sites for C4b and M proteins are only overlapping, but not identical. Furthermore, M proteins were able to displace C4BP from immobilized C4b, whereas C4b only weakly affected binding of C4BP to immobilized M proteins. We found that the molecular mechanisms involved in these two interactions differ because the binding between M proteins and C4BP is relatively insensitive to salt in contrast to the C4BP-C4b binding. In addition, six mAbs directed against the α-chain interfered with C4b-C4BP interaction, whereas only two of them efficiently inhibited binding of C4BP to M proteins. Collectively, our results suggest that binding between C4b and C4BP is governed mostly by electrostatic interactions, while additional noncovalent forces cause tight binding of C4BP to streptococcal M proteins.

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Section: Discussionmentioning

confidence: 99%

Human C4b-Binding Protein Has Overlapping, But Not Identical, Binding Sites for C4b and Streptococcal M Proteins

Blom

Berggård

Webb

et al. 2000

The Journal of Immunology

104

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“…Regarding the specificity of cofactors, it is generally accepted that FH acts on C3b, and C4BP on C4b, while CRI and MCP act on both. However, FH can act as a cofactor for C4b breakdown, although the activity is seen only at low salt strength and low pH (Seya et al, 1995). C4BP, similarly can act as cofactor for C3b breakdown (Blom et al, 2003;Seya et al, 1995;Sim et al, 1981).…”

Section: Fimentioning

confidence: 99%

Complement factor I in health and disease

Nilsson

Sim

Lea

et al. 2011

Molecular Immunology

140

112

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“…Fresh chicken and human sera were obtained from each species by standard methods (11,21). All samples were stored at Ϫ80°C immediately after collection until use.…”

Section: Ab Cells Human Proteins and Serummentioning

confidence: 99%

Regulator of Complement Activation (RCA) Locus in Chicken: Identification of Chicken RCA Gene Cluster and Functional RCA Proteins

Oshiumi

Shida

Goitsuka

et al. 2005

The Journal of Immunology

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A 150-kb DNA fragment, which contains the gene of the chicken complement regulatory protein CREM (formerly named Cremp), was isolated from a microchromosome by screening bacterial artificial chromosome library. Within 100 kb of the cloned region, three complete genes encoding short consensus repeats (SCRs, motifs with tandemly arranged 60 aa) were identified by exon-trap method and 3′- or 5′-RACE. A chicken orthologue of the human gene 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2, which exists in close proximity to the regulator of complement activation genes in humans and mice, was located near this chicken SCR gene cluster. Moreover, additional genes encoding SCR proteins appeared to be present in this region. Three distinct transcripts were detected in RNA samples from a variety of chicken organs and cell lines. Two novel genes named complement regulatory secretory protein of chicken (CRES) and complement regulatory GPI-anchored protein of chicken (CREG) besides CREM were identified by cloning corresponding cDNA. Based on the predicted primary structures and properties of the expressed molecules, CRES is a secretory protein, whereas CREG is a GPI-anchored membrane protein. CREG and CREM were protected host cells from chicken complement-mediated cytolysis. Likewise, a membrane-bound form of CRES, which was artificially generated, also protected host cells from chicken complement. Taken together, the chicken possesses an regulator of complement activation locus similar to those of the mammals, and the gene products function as complement regulators.

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Human factor H and C4b-binding protein serve as factor I-cofactors both encompassing inactivation of C3b and C4b

Cited by 41 publications

References 36 publications

Human C4b-Binding Protein Has Overlapping, But Not Identical, Binding Sites for C4b and Streptococcal M Proteins

Human C4b-Binding Protein Has Overlapping, But Not Identical, Binding Sites for C4b and Streptococcal M Proteins

Complement factor I in health and disease

Regulator of Complement Activation (RCA) Locus in Chicken: Identification of Chicken RCA Gene Cluster and Functional RCA Proteins

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