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

R E Hill, P H Shaw, P A Boyd, H Baumann, N D Hastie

Research output: Contribution to journalArticlepeer-review

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 alpha 1-antitrypsin, more appropriately called alpha 1-proteinase inhibitor (alpha 1-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 proteases. We show, surprisingly, that contrapsin is highly homologous to human alpha 1-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 alpha 1-antichymotrypsin are the descendents of a single gene that have evolved since rodent and primate divergence to encode proteins with different functions.

Original languageEnglish
Pages (from-to)175-7
Number of pages3
JournalNature
Volume311
Issue number5982
DOIs
Publication statusPublished - 13 Sep 1984

Keywords

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Biological Evolution
  • Chymotrypsin
  • Humans
  • Mice
  • Protease Inhibitors
  • Serpins
  • Trypsin Inhibitors
  • alpha 1-Antichymotrypsin

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