A close-up view of codon selection in eukaryotic initiation

Figures & data

Figure 1. Structural overview of the eukaryotic initiation complex (A) Small subunit of the eukaryotic ribosome (gray) showing the initiation factors eIF1 (red), eIF1A (orange) and eIF2-α (purple) in complex with initiator tRNA (blue) bound to the AUG start codon (green). The transparent sphere on top of the P-site is the volume where the simulations are focused. (B) A close-up view onto the mRNA-tRNA_i complex in surface representation illustrating the proximity of the initiation factors to the codon-anticodon minihelix. (C) A zoomed in view of the codon-anticodon triplet is represented as blocks using the standard reference frame for nucleic acids. eIF1 can be seen to bind closer to the first codon position toward the E-site while eIF1A is located in the A-site closer to the third codon position. The rRNA and proteins are omitted for clarity.

Table 1. Binding free energy penalties (kcal/mol) for mutating the canonical AUG start codon to near-cognate codons at the three codon positions.^a

	First		Second		Third
	GUG	CUG	ACG	AAG	AUA	AUC
+ eIFs	7.77 ± 0.44	5.21 ± 0.47	6.25 ± 0.20	8.40 ± 0.65	6.48 ± 0.50	6.86 ± 0.54
− eIF1	2.76 ± 0.48	5.50 ± 0.47	7.17 ± 0.45	4.40 ± 0.80	5.76 ± 0.54	6.54 ± 1.00
− eIFs	2.80 ± 0.41	3.75 ± 0.44	6.11 ± 0.31	3.24 ± 0.36	3.10 ± 0.41	5.30 ± 1.01
− Ribosome	4.19 ± 0.32		4.69 ± 0.23		2.55 ± 0.19

^a The case where both eIF1 and eIF1A are included is denoted by +eIFs, while −eIF1 and −eIFs represent the results without eIF1 or when both factors are missing, respectively. The last row shows the calculated intrinsic free energy penalties, for just the mRNA-tRNA_i codon-anticodon complex in aqueous solution.