EGF domains

EGF-domains External growth factor but general protein assembly control e.g. fibrillin... 

Schnepp, B., Donaldson, T., Grumbling, G., Ostrowski, S., Schweitzer, R., Shilo, B. Z., and Simcox, A. (1998). EGF domain swap converts a Drosophila EGF receptor activator into an inhibitor. Genes Dev., 12, 908-913. 

Yin Tissue Factor (TF) appears as the result of the duplication of a gene for [another protein] that binds EGF domains. The new gene product only comes into contact with the blood or hemolymph after tissue damage. 

Yang Prothrombin appears in an ancient guise with EGF domain(s) attached, the result of a. .. protease gene duplication and. .. shuffling. The EGF domain serves as a site for attachment to and activation by the exposed TF. 

Divorce Prothrombin engages in an exchange [of gene piecesl that leaves it with [domains] for binding to fibrin in place of its EGF domains, which are no longer needed for interaction with TF. ... 

Once all the violations have been checked and some corrections have been made, the process of structure calculation starts all over again with a new, improved restraint list. It may take more than 20 cycles of calculation and reexamination of NMR data before the restraint violations are reduced to a minimum. The results of this process after 27 cycles of calculation are shown in Figure 12.37 for Heregulin-o EGF domain. The average of the 20 lowest energy structures is shown on the left side, and on the right side is the same structure rotated a bit about the vertical axis. The major /3-sheet (3-6,17-24,30-37) is clearly visible but is twisted in the 3D structure. A short a-helix is inserted between two strands of the /1-sheet, and a minor two-strand /i-shccl (39 11,46 19) is seen at the top. Residues 51-63 are disordered and are not shown in the figure. 

Nrg1tmlcbm Targeted mutation 1, Carmen Birchmeier A neomycin resistance gene replaces exons 9,10, and 11, which encode the carboxy-terminus of the EGF domain of all known Nrgl variants... 

Nrg1tmlGne Targeted mutation 1, Genentech Replacement of the exon encoding the N-terminal half of the EGF domain with a neomycin cassette. This null mutation results in disruption of all splice forms of Nrgl... 

Nrg1tm2Cbm Targeted mutation 2, Carmen Birchmeier Exon 8 is fused to a lacZ gene. Coding sequences downstream of the fusion point, including the N-terminal half of the EGF domain, are deleted... 

Wen D, Peles E, Cupples R, Suggs SV, Bacus SS, et al. 1992. Neu differentiation factor A transmembrane glycoprotein containing an EGF domain and an immunoglobulin homology unit. Cell 69 559-572. 

The structure with eco also visualizes the Gla domain in a previously unseen conformation. One EGF domain is not visible in the structure, so the Gla domain seems to float in space distant from the protease (Fig. 7.4). Mg " ions present in the crystallization buffer bind to the Gla domain in an intermediate conformation, filling the three high affinity and low specifidty sites. This creates a domain that is primed for formation of the omega membrane-binding loop with the addition of Ca " to the remaining low affinity sites. 

A large protein family that contains extracellular domains homologous to EGF is called the EGF-domain proteins. EGF-like domains or modules are often found in many extracellular and membrane proteins (>70). They are involved in blood coagulation, fibrinolysis and the complement systems, matrix proteins, cell surface receptors, the low-density hpoprotein receptor and the developmentally important receptor. Notch. EGF-like domains may exist as multiple copies within proteins such as in the Drosophila protein Notch with 36 copies or as a single copy as in EGF itself It can also be found in conjunction with other modules. 

O-fucose is an important modification that mediates cell-cell interactions and leads to intracellular signaling events. Fucose is linked to either serine or threonine found in the consensus sequence C2XXGGS/TC3. The best-characterized modification sites are in the EGF domain of Notch (113). 0-Fuc is added by protein O-fucosyltransferase (0-FucT-I) and may be either a standalone modification or further extended. If extended. 

---