Structural Insights into Parasite eIF4E Binding Specificity

The eukaryotic translation initiation factor eIF4E recognizes themRNA cap, a key step in translation initiation. Here we have characterized eIF4E from the humanparasite Schistosomaman-soni. Schistosome mRNAs have either the typical monomethyl-guanosine (m7G) or a trimethylguanosine (m2,2,7G) cap derived from spliced leader trans-splicing. Quantitative fluorescence titration analyses demonstrated that schistosome eIF4E has similar binding specificity for both caps. We present the first crystal structure of an eIF4E with similar binding specificity for m7G and m2,2,7G caps. The eIF4E"m7GpppG structure demon-strates that the schistosome protein binds monomethyl cap in a manner similar to that of single specificity eIF4Es and exhibits a structure similar to other known eIF4Es. The structure suggests an alternate orientation of a conserved, key Glu-90 in the cap-binding pocket that may contribute to dual binding specificit