We have isolated and partially characterized a previously unrecognized protease-sensitive plasma protein identified during the development of a new protocol for the purification of human C2. This new protein is physicochemically similar to C2. It co- precipitated with C2 on polyethylene glycol (PEG) fractionation and specifically and independently bound, like C2, to Sepharose bound iC4/C4b. Like C2 this protein was cleaved in plasma or serum to immunochemically distinct fragments of beta (90kDa) and alpha (30kDa) mobility that may lose the capacity to bind to iC4 and/or C4b. The purified protein has a chain structure similar to C2 as determined by SDS-PAGE in the presence or absence of reducing agent and has a molecular mass of 120 kDa only somewhat greater than C2 at 95 kDa. C2 has been shown to contain about 16% N-linked carbohydrates. Using independent techniques, we have identified 16.8% N-linked sugar in C2 and 14.2% in gp120 kDa although the glycosylation pattern was different in the two proteins. Both proteins were shown to contain 6% sialic acid. Both proteins radioiodinated under similar conditions to the same specific activities with each of two different methods that produced 10-fold disparate results. These proteins have immunochemical similarities as well. Although monospecific anti-serum to each did nor cross- immunoprecipitate by standard gel techniques, anti-gp120 kDa serum did specifically identify shared epitopes by Western blot analysis. Mancini analysis identified 250-300 ug/ml of gp120 kDa in plasma. Initial studies suggested that the contact system protease Kallikrein is responsible for the rapid cleavage of gp120 kDa when stored in glass tubes at 4 degrees C in normal and HAE plasmas. It will be important to confirm the protease responsible for gp120 kDA cleavage and to isolate the fragments to pursue biological and functional studies in vitro and in animals (see project #Z01 AI 00278-06 LCI). Since C2 is a member of a recently described class of C4b/C3b binding proteins which contain a 60-amino-acid repeat sequence, it will be of interest to determine if gp120 kDa is also a member of this class of proteins.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Intramural Research (Z01)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Niaid Extramural Activities
United States
Zip Code