Article: On the Origins of Chemical Biodefense
- From: "Robert Karl Stonjek" <rstonjek@xxxxxxxxxxxxxx>
- Date: Sun, 16 Oct 2005 01:41:04 -0400 (EDT)
On the Origins of Chemical Biodefense
The following points are made by R. Liddington and L. Bankston (Nature 2005
437:484):
1) Before antibodies evolved, primitive multicellular organisms devised a
general defense system against bacterial and viral invaders called "innate
immunity". The system has survived in vertebrates with its core components
little changed during the intervening 700 million years[1]. A central
element of this defense strategy is an activated thioester -- a molecular
warhead -- that is today used only in this setting, perhaps because it is
potentially so destructive. The protein C3, a member of a small family of
related proteins carrying this warhead, is a large molecule of the
"complement" system, which identifies foreign agents and targets them for
destruction. New work presents the atomic-resolution crystal structure of
C3, as well as that of an inactivated fragment, C3c.
2) From the structure of C3, it is immediately apparent how this large
multi-domain protein evolved from a series of simpler building-blocks into a
tightly regulated killing machine. First, the core of C3 is composed of
eight copies of a simple three-dimensional motif, which Gros et al term
"macroglobulin" (MG1-MG8), arranged in tandem. The presence of these
repeated domains suggests that the core arose through duplications of a
primordial gene that originally encoded a single domain. Random mutations
occurring over hundreds of millions of years mean that the component
amino-acid sequences of individual domains no longer share any similarity;
nevertheless, their evolutionary origin is preserved in their
three-dimensional structure.
Full text at ScienceWeek
http://scienceweek.com/2005/sw051021-5.htm
Posted by
Robert Karl Stonjek
.
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