Modulation of C3b Hemolytic Activity by a Plasma Protein Distinct from C3b Inactivator

Whaley, K; Ruddy, Shaun

doi:10.1126/science.948757

Cited by 151 publications

(70 citation statements)

References 18 publications

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“…SCR [8][9][10][11][12][13][14][15][16][17][18][19][20] or the two most C-terminal SCRs of fH and with recombinant FHR-3 and FHR-4. A representative purification of the His-tagged recombinant proteins by nickel chelate chromatography is shown for the SCR 19-20 construct (Figure 2).…”

Section: Presence Of Binding Epitopes In Truncated Fragments Of Fh Anmentioning

confidence: 99%

“…Among the members of the H protein family, complement regulatory functions have been described for fH [5] and FHL-1 [6,7], but not for any of the FHR proteins. fH and FHL-1 act as cofactor for factor-I-mediated degradation of C3b, and both proteins have decay-accelerating activity [6][7][8][9]. In addition, both proteins possess heparin-binding domains, and, for fH, additional binding sites for C3b and heparin are reported to be located at the C-terminus of the protein [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

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The C-terminus of factor H: Monoclonal antibodies inhibit heparin binding and identify epitopes common to factor H and factor-H related proteins

Prodinger

Hellwage

Spruth

et al. 1998

Molecular Immunology

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Section: Presence Of Binding Epitopes In Truncated Fragments Of Fh Anmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The C-terminus of factor H: Monoclonal antibodies inhibit heparin binding and identify epitopes common to factor H and factor-H related proteins

Prodinger

Hellwage

Spruth

et al. 1998

Molecular Immunology

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“…Whaley and Ruddy (4) have identified j1H as the component that effects active disassembly of the enzymes. They also demonstrated (5) that f#1H accelerates the action of C3b inactivator on C3b. An absolute requirement of f#1H for the action of C3b inactivator (C3bINA) on fluid-phase C3b was demonstrated in this laboratory (6).…”

mentioning

confidence: 99%

Initiation of the alternative pathway of complement: recognition of activators by bound C3b and assembly of the entire pathway from six isolated proteins.

Schreiber¹,

Pangburn²,

Lesavre³

et al. 1978

Proc. Natl. Acad. Sci. U.S.A.

147

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ABSTRACr An intact alternative pathway of complement activation was assembled from six isolated proteins present at their respective physiological concentrations (C3, 1200 ug/ml; factor B, 200 ttg/ml; factor D, 2 Aig/ml; 311H, 560 Wig/ml; C3b inactivator, 34 gg/ml; and native properdin, 20 jg/ml) Initiation of the pathway required the presence of five of these proteins not including properdin. The initial C3 convertase of the system was shown to be a fluid-phase rather than a surface-bound enzyme. The ability of the pathway to discriminate between activator and nonactivator was found to reside in the bound C3b molecule. When bound to the surface of an activator through its labile binding site, C3b interacts with surface structures of the activator through another site on the molecule.This interaction results in diminished jPlH binding to C3b and thereby allows the bound C3b molecule to escape control and participate in C3 convertase formation. Thus, initiation of the alternative pathway is a two-step process, the first being nonspecific and the second being discriminatory. (7,8) made the crucial observation that both C3b and the resultant CS convertase deposited on the surface of activators are relatively protected from destruction by the regulatory proteins. In this laboratory it was shown that protection of bound C3b is due to restriction of #1H binding to C3b. It was further shown that restriction of control could be generated by defined chemical rndifications of a nonactivator thereby converting it to an actimtor (9-11). These findings aid in explaining the known ability of activators to allow amplification of the pathway in the presence of the controlling proteins.

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“…Factor H is one of the control proteins of the complement system (Whaley & Ruddy, 1976). It is an abundant single-chain plasma glycoprotein (Mr approx.…”

Section: Introductionmentioning

confidence: 99%

Complement factor H-binding protein of Raji cells and tonsil B lymphocytes

Erdei

Sim

1987

Biochemical Journal

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Several reports have indicated that Factor H has specific effects on certain cell populations, suggesting that Factor H receptors may exist. Lambris & Ross [(1982) J. Exp. Med. 155, 1400-1411] purified a protein from Raji B-lymphoblastoid cell culture supernatants, using Factor H-Sepharose affinity chromatography. This species appeared to consist of two disulphide-linked components each of Mr 50,000, with an additional 50,000-Mr chain attached non-covalently. The existence of cell-surface Factor H-binding proteins has now been re-investigated with 125I surface-labelled Raji and tonsil B cells. Non-ionic-detergent extracts of the cells, in 0.1% Nonidet P40/10 mM-sodium phosphate buffer, pH 7.4, were incubated with Factor H-Sepharose in the presence of proteinase inhibitors. After the beads had been washed, bound components were eluted with 50 mM-NaCl. A single radioactive species was eluted from the resin, which migrates identically with Factor H (apparent Mr 170,000) in SDS/polyacrylamide-gel electrophoresis under reducing and non-reducing conditions. Biosynthetic radiolabelling studies confirmed that this species was synthesized by Raji cells. Examination of culture supernatants from biosynthetically radiolabelled Raji cells showed again the presence of a single soluble species that bound to Factor H-Sepharose, but this species was of lower Mr (approx. 105,000) than the membrane-derived protein. The soluble form may be produced by proteolysis of the membrane form, or may be of separate origin. The similarity in size of the cell-surface protein to Factor H was initially confusing, but it is distinct from cell-surface Factor H on the basis of three criteria: (1) it is not recognized by anti-)2 anti-(Factor H); (2) it does not bind to Zn2+-chelate resin, whereas Factor H does; (3) cell-surface Factor H present on U937 cells does not bind to Factor H-Sepharose.

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Modulation of C3b Hemolytic Activity by a Plasma Protein Distinct from C3b Inactivator

Cited by 151 publications

References 18 publications

The C-terminus of factor H: Monoclonal antibodies inhibit heparin binding and identify epitopes common to factor H and factor-H related proteins

The C-terminus of factor H: Monoclonal antibodies inhibit heparin binding and identify epitopes common to factor H and factor-H related proteins

Initiation of the alternative pathway of complement: recognition of activators by bound C3b and assembly of the entire pathway from six isolated proteins.

Complement factor H-binding protein of Raji cells and tonsil B lymphocytes

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