2i2O Protein Structure Presentation

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Materials and Methods

1) Protein search on PDB, NCBI Entrez, Pfam and InterPro databases

  • PDB code used: 2i2o

2) Identifying other similar structures with DALI server

3) Comparing the identified structures using CE comparison



Figure 3.0 Structure of MIF4G (PDB:1hu3)

- Protein was isolated form Danio rerio and expressed in Escherichia coli.

- Structure has similarities with the “Eukaryotic Translation Initiation Factor 4G (eIF4G)” protein.

- Protein has 2 chains; and consists of nickel (Ni2+) and selenomethionine (C5H11NO2Se) components.

Pfam and InterPro

- Identified as "Middle domain of eIF4G", termed MIF4G.

- Consists essentially of alpha helices and has “multiple alpha-helical repeats”. Within eIF4G, it binds to the RNA helicase eIF4A, eIF3, RNA and DNA.

DALI results

    1. SUMMARY: PDB/chain identifiers and structural alignment statistics
  1: 3028-A 2i2o-A 37.1  0.0  206   206  100      0      0     1 S    STRUCTURAL GENOMICS, UNKNOWN FUNCTION 	eif4g-like prote
  2: 3028-A 1hu3-A 15.2  2.7  164   204   23      0      0    12 S     TRANSLATION 	eif4gii fragment (eukaryotic initiation f
  3: 3028-A 1uw4-B 10.9  3.6  164   247    9      0      0    12 S    NONSENSE MEDIATED MRNA DECAY PROTEIN 	regulator of nons
  4: 3028-A 1h6k-A 10.6  3.9  175   728   11      0      0    11 S     NUCLEAR PROTEIN 	cbp80 fragment (ncbp 80 kda subunit, 
  5: 3028-A 2db0-A  8.1  3.3  148   239   14      0      0    13 S    PROTEIN BINDING 	253aa long hypothetical protein (hypot
  6: 3028-A 1b3u-A  8.0 27.7  150   588   13      0      0    13 S    SCAFFOLD PROTEIN 	protein phosphatase pp2a fragment

CE Structural comparison

- 1hu3 and 2i2o: Alpha-helices between 2i2o and 1hu3 were folded in same orientation

- 1h6k and 2i2o: N-terminal region of 1h6k displayed similarity with 2i2o; hence a possibility that MIF4G protein is a region, or even an active domain, near the N-terminal of the nuclear cap binding protein complex (CBC).


Figure 4.0 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 4.1 CE Comparison of the zebrafish putative MIF4G(blue) and human MIF4G(pink). Arrows indicate grooves which C’ terminal linker segment can wrap around domain

- Protein of interest is highly similar in structure to human MIF4G (PDB: 1hu3). Therefore, MIF4G can be utilised as a model to formulate predictions on its structure.

- The 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 (Marintchev & Wagner 2005).

  • Protein has an overall crescent shape. Helical hairpins are stacked on top of the other to confer this 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, 2001).

- MIF4G is one of the 3 domains on eIF4G RNA regulatory protein. Each of these domains are connected by linkers.

  • eIF4G has 3 domains: MIF4G, MA3 and W2

- 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 (Marintchev & Wagner 2005). This will account to an extent the presence and potential function of the numerous grooves observed in the domain structure.


- All further hypotheses on structural organization and interactions of the domain within the eIF4G protein necessitate additional analysis.