Biology Reference
In-Depth Information
technologies and in vivo animal models, we have been able to verify
and also predict the activity of a new generation of complement
inhibitors and provide a versatile platform for developing effective
complement therapeutics. Furthermore, unique, species-specific com-
plement reagents have been developed that will help us study
C3-mediated effects in mouse models of disease and determine those
structural modules that are responsible for these functions [93]. The use
of proteomic analysis, as a novel tool for probing protein-protein inter-
actions, has produced evidence that complement can interact with
networks that affect complex developmental processes, such as liver
regeneration. In conclusion, all these diverse studies are integrated
under the unifying theme of evolution that provides further insight
into the molecular aspects of complement function and underscores
the fact that complement—despite its ancient origin—has evolved into
a versatile and yet “unpredictable” innate immune system.
ACKNOWLEDGMENTS
This research was supported by National Institutes of Health Grants AI 30040,
GM-56698, GM-62134, and DK-059422.
Limited portions of this material appeared in
Molecular Immunology
, 41
(2004) 153-64 (reproduced by permission of Elsevier), and in a special issue
of
Immunological Research
: Immunology at Penn, 7 (2003) 367-85.
REFERENCES
1. Hood, L. and D. Galas. The digital code of DNA.
Nature
, 421(6921):444-8,
2003.
2. Hood, L. Systems biology: integrating technology, biology, and computation.
Mechanisms of Ageing and Development
, 124(1):9-16, 2003.
3. Mastellos, D. and J. D. Lambris. Complement: more than a “guard” against
invading pathogens?
Trends in Immunology
, 23(10):485-91, 2002.
4. Lambris, J. D. The multifunctional role of C3, the third component of com-
plement.
Immunology Today
, 9(12):387-93, 1988.
5. Sahu, A. and J. D. Lambris. Structure and biology of complement protein
C3, a connecting link between innate and acquired immunity.
Immunological
Reviews
, 180:35-48, 2001.
6. Muller-Eberhard, H. J. Molecular organization and function of the comple-
ment system.
Annual Reviews in Biochemistry
, 57:321-47, 1988.
7. Nagar, B., R. G. Jones, R. J. Diefenbach, et al. X-ray crystal structure of C3d:
a C3 fragment and ligand for complement receptor 2.
Science
, 280(5367):
1277-81, 1998.
8. Prota, A. E., D. R. Sage, T. Stehle, et al. The crystal structure of human CD21:
implications for Epstein-Barr virus and C3d binding.
Proceedings of the
National Academy of Sciences USA
, 99(16):10641-6, 2002.
9. Szakonyi, G., J. M. Guthridge, D. Li, et al. Structure of complement receptor
2 in complex with its C3d ligand.
Science
, 292(5522):1725-8, 2001.
Search WWH ::
Custom Search