Evolution of distinct EGF domains with specific functions
- 1 April 2005
- journal article
- Published by Wiley in Protein Science
- Vol. 14 (4), 1091-1103
- https://doi.org/10.1110/ps.041207005
Abstract
EGF domains are extracellular protein modules cross‐linked by three intradomain disulfides. Past studies suggest the existence of two types of EGF domain with three‐disulfides, human EGF‐like (hEGF) domains and complement C1r‐like (cEGF) domains, but to date no functional information has been related to the two different types, and they are not differentiated in sequence or structure databases. We have developed new sequence patterns based on the different C‐termini to search specifically for the two types of EGF domains in sequence databases. The exhibited sensitivity and specificity of the new pattern‐based method represents a significant advancement over the currently available sequence detection techniques. We re‐annotated EGF sequences in the latest release of Swiss‐Prot looking for functional relationships that might correlate with EGF type. We show that important post‐translational modifications of three‐disulfide EGFs, including unusual forms of glycosylation and post‐translational proteolytic processing, are dependent on EGF subtype. For example, EGF domains that are shed from the cell surface and mediate intercellular signaling are all hEGFs, as are all human EGF receptor family ligands. Additional experimental data suggest that functional specialization has accompanied subtype divergence. Based on our structural analysis of EGF domains with three‐disulfide bonds and comparison to laminin and integrin‐like EGF domains with an additional inter‐domain disulfide, we propose that these hEGF and cEGF domains may have arisen from a four‐disulfide ancestor by selective loss of different cysteine residues.Keywords
This publication has 60 references indexed in Scilit:
- The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003Nucleic Acids Research, 2003
- The Protein Data BankNucleic Acids Research, 2000
- Solution structure of an EGF module pair from the Plasmodium falciparum merozoite surface protein 1Journal of Molecular Biology, 1999
- Crystal Structure of Three Consecutive Laminin-type Epidermal Growth Factor-like (LE) Modules of Laminin γ1 Chain Harboring the Nidogen Binding SiteJournal of Molecular Biology, 1996
- Efficient Association of an Amino-terminally Extended Form of Human Latent Transforming Growth Factor-β Binding Protein with the Extracellular MatrixJournal of Biological Chemistry, 1995
- SCOP: A structural classification of proteins database for the investigation of sequences and structuresJournal of Molecular Biology, 1995
- CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choiceNucleic Acids Research, 1994
- Basic local alignment search toolJournal of Molecular Biology, 1990
- Carbohydrate composition and presence of a fucose-protein linkage in recombinant human pro-urokinaseBiochemical and Biophysical Research Communications, 1990
- Dictionary of protein secondary structure: Pattern recognition of hydrogen‐bonded and geometrical featuresPeptide Science, 1983