Global Conformational Changes of Ribosome Observed by Normal Mode Fitting for 3D Cryo-EM Structures

Many three-dimensional density maps of 70S ribosome at various functional states are available now in the Electron Microscopy DataBank at EBI. We used our new flexible-fitting approach to systematically analyze these maps to reveal the global conformational differences between the EM structures. Large-scale ratchet-like deformations were observed in an EM structure of the initiation complex and in some EM structures bound with EFG, RF3, and RRF. In most of them, the L1 stalk, which interacts with the tRNA molecule at the E site of ribosome and is considered to be involved in the release of the tRNA, was in the blocking state for the E-tRNA. Furthermore, we found that the EM structures bound with EFG or RRF were aligned in the conformational space, suggesting that the large-scale conformational changes of the 70S ribosome bound with these factors occur along a specific pathway in a concerted manner.