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Plasma protease inhibitors in mouse and man: divergence within the reactive centre regions

Abstract

The plasma protease inhibitors control a wide variety of physiological functions including blood coagulation, complement activation and aspects of the inflammatory response. The inhibitors function by forming a 1:1 complex with a specific protease within the reactive centre region of the inhibitor. Little is known about the evolutionary relationships of these inhibitors. We report here the sequences of cDNAs which represent the C-terminal halves of the two major murine plasma protease inhibitors. One of these, murine α1-antitrypsin, more appropriately called α1-proteinase inhibitor (α1-PI), has diverged from its human counterpart at a vital position in the reactive centre but this has not led to a physiologically significant change in function. Also, we have determined the partial sequence of a recently characterized protein termed contrapsin, which inhibits trypsin-like proteases1,2. We show, surprisingly, that contrapsin is highly homologous to human α1-antichymotrypsin, an inhibitor of chymotrypsin-like proteases. The reactive centre regions of these two inhibitors have diverged considerably, which may account for the differences in specificity. We propose that the genes for contrapsin and human α1-antichymotrypsin are the dependents of a single gene that have evolved since rodent and primate divergence to encode proteins with different functions.

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Hill, R., Shaw, P., Boyd, P. et al. Plasma protease inhibitors in mouse and man: divergence within the reactive centre regions. Nature 311, 175–177 (1984). https://doi.org/10.1038/311175a0

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