2i2O Discussion

A Twisted Protein -- Structure of the MIF4G Figure 2: MIF4G, viewed along the cylindrical axes of the alpha helices. (Marcotrigiano et al.) Each colour represents an alpha helix hairpin. Black line indicates a groove between two hairpins. Enlarge Figure 2: MIF4G, viewed along the cylindrical axes of the alpha helices. (Marcotrigiano et al.) Each colour represents an alpha helix hairpin. Black line indicates a groove between two hairpins. Figure 3:CE Comparison of the zebrafish putative MIF4G(blue) and human MIF4G(pink). Arrows indicate grooves which C’ terminal linker segment can wrap around domain Enlarge Figure 3:CE Comparison of the zebrafish putative MIF4G(blue) and human MIF4G(pink). Arrows indicate grooves which C’ terminal linker segment can wrap around domain

The above results demonstrate a parallel, highly similar structure of eIF4G-like protein to human MIF4G (PDB: 1hu3). While there is a lack of conclusive studies and evidence on our protein of interest, the established protein MIF4G can be utilised as a model to formulate predictions on its structure. According to Wagner et al., MIF4G contains five helical hairpins oriented in a right-handed solenoid, and is similar to the HEAT [Huntingtin, elongation factor 3, a subunit of protein phosphatase 2A (PP2A), and target of rapamycin] domain (Wagner et al). The overall protein resembles a crescent, with its superhelical axis perpendicular to the cylindrical axes of the alpha helices (Marcotrigiano et al.). The helical hairpins are stacked one on top of the other to confer the protein its overall crescent shape.

MIF4G binds to eIF4A, an RNA helicase, and RNA, hence rendering its role in regulating cell translation. A protease-resistant region identified by proteolysis and mass spectrometry is speculated to be the binding site for eIF4A (marcotrigiano et al.).

MIF4G is one of the three domains present on eIF4G RNA regulatory protein. eIF4G has three domains, MIF4G, MA3 and W2, which are connected by linkers (Wagner et al.). It was hypothesized that the C’ terminal linker segment of MIF4G interacts with the domain by wrapping around the inter-helical grooves of the domain (Wagner et al.). This will account to an extent the presence and potential function of the numerous grooves observed in the domain structure.

All in all, information regarding the structure of eIF4G-like protein (our protein of interest) is limited to the current knowledge of its MIF4G homologue. Any further hypotheses on structural organization and interactions of the domain within the eIF4G protein necessitate additional analysis.

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