Serine proteinase inhibitors from nematodes and the arms race between host and pathogen
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Date
2001Author
Zang, Xingxing
Maizels, Rick
Metadata
Abstract
Parasite nematode genomics is a relatively new
field9, but already two of the most interesting gene
families to be found encode serine proteinase
inhibitors. This article describes a family of nematode
proteinase inhibitors with homology to mammalian
serpins, as well as a distinct set of lower-molecularweight
inhibitors first discovered by biochemical
analysis of the human roundworm Ascaris10.Taking
these two examples into account, it thus appears that
parasitic nematodes have evolved two parallel
strategies for interfering with mammalian serine
Serine proteinase inhibitors are encoded by a large gene family of long
evolutionary standing. Recent discoveries of parasite proteins that inhibit
human serine proteinases, together with the complete genomic sequence from
Caenorhabditis elegans, have provided a set of new serine proteinase inhibitors
from more primitive metazoan animals such as nematodes. The structural
features (e.g. reactive centre residues), gene organization (including intron
arrangements) and inhibitory function and targets (e.g. inflammatory and
coagulation pathway proteinase) all contribute important new insights into
proteinase inhibitor evolution. Some parasite products have evolved that block
enzymes in the mammalian host, but the human host responds with a
significant immune response to the parasite inhibitors. Thus, infection produces
a finely balanced conflict between host and pathogen at the molecular level, and
this might have accelerated the evolution of these proteins in parasitic species
as well as their hosts.