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Extinction Coeff： A280 nm = 1.03 at 1.0 mg/mL
Molecular Weight: ~1,030,000 Da (~13 chains)
General Description Vitronectin (S Protein) binds to membrane attack complexes that fail to insert into membranes. The result is a soluble complex of S Protein and C5b-9 and this has been named SC5b-9 (Dodds, A.W. and Sim, R.B. (1997)). Activation of complement in the absence of bilipid layer membranes results in most of the activated C5 forming SC5b-9 complexes. This can occur with activating particles such as immune complexes, yeast and bacterial cell walls. The SC5b-9 complexes can have more than one C9 (usually three) and more than one S Protein (usually three) per complex. Thus, the typical molecular weight is ~1,030,000 Da. One C5b-7 complex can bind up to three molecules of S Protein. If C8 or C8 and C9 have already bound to the C5b-7 complex three S Protein molecules will bind to these complexes as well. The C5b6 and C5b-7 complexes sometimes diffuse away from the target cell and enter the membrane of a nearby cell. This is called bystander lysis or “reactive lysis” and can be a significant source of pathology. Binding of S Protein blocks this non-specific lysis. Diffusion of these early complexes away from the activating surface may result in addition of C8 and C9 to the complex prior to S Protein binding. Once S Protein binds to these complexes it prevents their membranolytic functions, thuscreating soluble complexes that are subsequently cleared from circulation.
Physical Characteristics & Structure The molecular weight of SC5b-9 Complex has a maximum approximate molecular weight of 1,030,000 Da and it is composed of ~13 polypeptide chains. Variations in molecular weight may occur due to the fact that SC5b-9 complexes mayhave 1 to 3 C9 molecules and 1 to 3 S Protein molecules per complex.
Function See General Description above.
Assays SC5b-9 has no functional activity. Several commercial ELISA kits specific for SC5b-9 are available. These are sold by BD Biosciences, Technoclone Ltd, Quidel, andHyCult Biotechnology. Most rely on capture of the SC5b-9 with antibodies specific for neo-antigens on the complex and secondary detection with antibodies to complement proteins of the C5b-9 complex.
Applications See General Description above.
In vivo The normal serum concentration of SC5b-9 is low. Normal baseline levels for properly stored plasma range from less than 100 ng/mL to 600 ng/mL SC5b-9 or less than 0.1% of maximal conversion. Elevated levels of circulating SC5b-9 complexes have been associated with bacterial infections and other diseases where complement activation is known to occur.
Regulation SC5b-9 complexes form spontaneously and the process has no known regulators. S Protein does compete for newly formed C5b-9 with other lipid-binding molecules in plasma such as LDL and HDL. After formation SC5b-9 complexes are cleared from the circulation.
Deficiencies Deficiencies of C5, C6, C7, C8, C9 or S Protein will prevent formation of complete SC5b-9 complexes.
Diseases As stated above, deficiencies of C5, C6, C7, C8, C9 or S protein will prevent formation of complete SC5b-9 complexes. The inability to form MAC (C5b-9 complexes) is a serious problem due to the high susceptibility to bacterial infections. No known diseases are specifically associated with the inability to produce soluble SC5b-9 complexes.
Precautions/Toxicity/Hazards This protein is purified from human plasma, therefore precautions appropriate for handling any blood-derived product must be used even though the source was shown by certified tests to be negative for HBsAg, HTLV-I/II, STS, and for antibodies to HCV, HIV-1 and HIV-II. Hazard Code: B WGK Germany 3 MSDS available upon request. |
