Properdin

Robson, K.J., Hall, J.R., Jennings, M.W., Harris, T.J., Marsh, K., Newbold, C.I., Tate, V.E. and Weatherall, D.J. (1988) Ahighly conserved amino acid sequence in thrombospondin, properdin and in proteins from sporozoites and blood-stages of the human malaria parasite. Nature 335, 79-82. 

Reported applications of DST include the crosslinking of ubiquinone cytochrome C reductase (Smith et al., 1978), characterization of the cell surface receptor for colony-stimulating factor (Park et al., 1986), investigation of the Ca+2-, Mg+2-activated ATP of E. coli (Bragg and Hou, 1980), and characterization of human properdin polymers (Farries and Atkinson, 1989). 

Individuals with asplenia, complement deficiency, or properdin deficiency... 

In the alternative pathway of activation a small amount of C3b is formed and becomes bound to the cell surface. This binds another proenzyme factor B,165 which is converted by protease factor D166 to active protease Bb. The latter in its complex with C3b is the enzyme that cleaves C3 in large amounts and permits a rapid formation of more Bb and also of the complex (C3b)2 Bb P, which attacks C5 (Fig. 31-8). These complexes are stabilized by the abundant serum protein properdin (P).167... 

C3b is a dangerous protein to have floating around, since it can activate the destructive end of the complement pathway. In order to minimize random damage, two proteins (factors I and H), search out, stick to, and destroy C3b in solution. But if C3b is on the surface of a cell, then another protein (properdin), binds to and protects C3b from degradation so that it can do its job. How does C3b target foreign cells in the absence of antibodies C3b is effective only if it sticks to the surface of a cell. The chemical reaction by which it does so goes faster in the presence of the molecules typically found on the surface of many bacteria and viruses. ... 

Figure 15.1 Complement activation pathways. The classical, lectin and alternative pathways converge into a final common pathway when C3 convertase (C3 con) cleaves C3 into C3a and C3b. Ab = antibody, Ag = antigen, Cl-INH = Cl inhibitor, MAC = membrane attack complex, MASP = MBL-associated serine protease, MBL = mannose-binding lectin, P = properdin. Overbar indicates activation.

Human alternate complement pathway components /31H, C3bINA, factor B, and activated properdin (P)... 

It should be mentioned that injection of the endotoxins (lipopolysac-charides) of gram-negative bacteria also produces an increase of antibody titer, but this action is linked with the properdin system and is of a very... 

In RNase 2 the main stmctural roles of the C-linked mannose seem to be to stabilize the IV-terminal loop of the protein and to keep Trp7 in a specific orientation, compared to the non-C-glycosylated form [3]. Site-directed mutagenesis has revealed that the sequence Trp-x-x-Trp is required for the C-mannosylation of the first tryptophan [4]. This C-glycosidic linkage has been proved to occur also in a number of other mammalian proteins, such as interleukin-12, complements, properdin, thrombospondin, erythropoietin receptor, mucins, and a bovine lens protein [5,6,7,8,9,10,11]. It has been demonstrated that the C-mannosylation is an enzyme-catalyzed event [12]. 

Figure 7-2 Control of the alternative complement pathway by activating surfaces. When complement component C3b binds to a surface, there exist two possible outcomes. Under normal conditions, when no activating surface is present (e g., if C3b has contacted normal tissue), sequential addition of blood cofactors H and I converts C3b into C3c, inactivating the complement protein. If an activating surface such as a microbe or damaged tissue is encountered, sequential addition of factors B and D drives the alternative pathway to the normal properdin (P) intermediate, and the complement cascade is triggered. The properdin-containing component (C3bBbP) feeds back to the beginning of the pathway, generating more C3.

The alternative pathway, which includes C3, factors B and D, and properdin... 

The classical pathway is activated primarily by the antibody antigen complexes. In 1913, Browning and Mackie showed that cobra venom could trigger serum-mediated lysis of erythrocytes in the absence of an antibody. Pillemer described properdin as a component of the antibody-independent complement pathway in 1954, and proposed the name properdin pathway. His work was not accepted until the 1960s, however, when the alternative pathway was... 

Properdin Relatively rare X-linked neisserial infections... 

Properdin pathway) complex, C3 convertase (C3bBb) thioester with nucleophilic molecules on cell surfaces ... 

Ba Bb P (properdin) 20-30 -46,000 Chemotactic peptide Active site-containing chain of C3bBb, the C5 convertase Stabilizer of C3bBb... 

Also see color figure.) Initiation of actron by complement occurs via three pathways classical, alternative (properdin), and lectin pathways. 

P (properdin) can also bind to the C3 convertase. Its role is to stabilize the complex and hence it is considered a cofactor-activator in the alternative pathway. These components plus additional C3b molecules form the C5 convertase, an enzyme complex that peoteolytically converts C5 to C5a and CSb. Properdin stabilizes C3b and Bb in the complex and protects these proteins from proteolytic inactivation by factor I. Factor H competes for Bb in the C5 convertases, the same as it does in the C3 convertase. The alternative pathway has also been called the properdin pathway because of properdin s participation in alternative pathway C3 and C5 convertases. C5b is a component in the terminal complex of the complement activation process, the MAC. The MAC is composed of a self-assembled, noncovalent complex of C5b, C6, C7, C8, and C9. Together these components produce a pore-like structure that makes the membrane of the cell to which it is attached permeable and causes cell death. Under the electron microscope the MAC appears like an impact crater similar to those observed on the surface of the moon. C5a is also an anaphylatoxin like C3a, but it is more potent. C5a is also a chemokine and attracts phagocytic cells to the site of complement activation. 

Complement deficiencies are associated with several diseases. Alternative pathway deficiencies are rare, but when they exist more than one-half of factor D or properdin-deficient individuals suffer from Neisseria infections of which 75% are fatal. Individuals with deficiencies in the MAC components, e.g., C5, C6, Cl, and C8, are also susceptible to infection with Neisseria. Deficiencies in C1, C4, and C2 are associated with systemic lupus erythematosus and glomerulonephritis. Hereditary angioedema, a disease characterized by recurrent submucosal and subcutaneous edema, is caused by a deficiency in Cl inhibitor. Complexes and interactions similar to those of the complement system are also characteristic of the clotting system (Chapter 36). 

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