Analysis of the natural polymeric forms of human properdin and their functions in complement activation.
Many of the anomalies observed in studies or properdin may be explained on the basis of its ability to form a series of multi-subunit polymers and by differences in the functions of these forms of properdin. Dimers (P2), trimers (P3), tetramers (P4), and higher Mr polymers (Pn) of the 46,000-Da subunit were separated by gel filtration or by cation exchange chromatography of purified properdin. The specific activity of each form was measured in two assays. The native properdin activity of P4 was 10 times that of P2 (on a molar basis) with the order: P4 greater than P3 greater than P2 greater than Pn. During C activation P4 was found to be consumed first, P3 second, and P2 last, consistent with their measured specific activities. Assays for activated properdin showed that only Pn caused fluid phase C consumption when incubated in serum at normal concentrations. Pn accumulated during long term storage of purified P and freezing rapidly converted the smaller oligomers to Pn. The isolated oligomers were extremely stable, but did redistribute after denaturation-renaturation cycles by using low pH or guanidine. Renaturation after exposure of any species to denaturing conditions yielded mixtures of 20:54:26 (P4:P3:P2). This distribution was almost identical to that found in fresh normal human serum or plasma, suggesting that a distinct distribution of oligomers exists in blood that provides the C system with an apparently advantageous range of specific activities.
Pangburn
M K
MK
Department of Biochemistry, University of Texas Health Center, Tyler 75710.
D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D003167:Complement Activation; D003170:Complement Pathway, Alternative; D004795:Enzyme Stability; D006801:Humans; D046911:Macromolecular Substances; D008970:Molecular Weight; D010949:Plasma / Q000032:analysis; D011414:Properdin / Q000302:isolation & purification / Q000502:physiology*
D046911:Macromolecular Substances; D011414:Properdin