Does glutamine methylation affect the intrinsic conformation of the universally conserved GGQ motif in ribosomal release factors?

Abstract

The GGQ motif is the only universally conserved feature of ribosomal class 1 release factors. Mutational experiments and structural studies have suggested that the glutamine residue of the GGQ motif (Q185 in human eRF1 numbering) is critical for catalysis of the termination reaction on the ribosome. Furthermore, it has been established that Q185 is Nepsilon methylated in prokaryotes as well as eukaryotes, and that methylation significantly enhances the catalytic activity. It is, however, not known whether this methylation affects the intrinsic structure of the free release factor, which could be important for its interaction with the ribosome. In this work, we report molecular dynamics simulations, starting from 25 different NMR structures of human eRF1, in addressing this problem. The results show that there is no such structural effect on the free release factor caused by the Nepsilon methylation of Q185, suggesting that its role is intimately associated with the ribosome environment.