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Evolution of distinct EGF domains with specific functions
Merridee A Wouters1, Isidore Rigoutsos, Carmen K Chu
1Computational Biology and Bioinformatics Program, Victor Chang Cardiac Research Institute, 384 Victoria St., Darlinghurst, Sydney, NSW 2010, Australia. m.wouters@victorchang.unsw.edu.au
Protein Science : a Publication of the Protein Society
|March 18, 2005
Summary
Researchers identified two distinct types of epidermal growth factor (EGF)-like domains, human EGF-like (hEGF) and complement C1r-like (cEGF). This discovery links domain type to specific post-translational modifications and functions, advancing protein domain classification.
Area of Science:
- Biochemistry
- Structural Biology
- Bioinformatics
Background:
- Epidermal growth factor (EGF) domains are extracellular protein modules with three intradomain disulfides.
- Two types, human EGF-like (hEGF) and complement C1r-like (cEGF), are proposed but lack functional differentiation in databases.
Purpose of the Study:
- To develop methods for specifically identifying hEGF and cEGF domains.
- To investigate functional relationships and post-translational modifications associated with EGF domain subtypes.
Main Methods:
- Development of novel sequence patterns for specific detection of hEGF and cEGF domains.
- Re-annotation of EGF sequences in Swiss-Prot database.
- Structural analysis of EGF domains and comparison with related structures.
Main Results:
- New sequence patterns exhibit high sensitivity and specificity for differentiating EGF domain types.
- Post-translational modifications, including glycosylation and proteolytic processing, are subtype-dependent.
- hEGF domains are associated with cell surface shedding, intercellular signaling, and EGF receptor family ligands.
Conclusions:
- Functional specialization correlates with the divergence of hEGF and cEGF subtypes.
- Proposes an evolutionary model where hEGF and cEGF domains originated from a four-disulfide ancestor through selective cysteine loss.