Figure 11. Proposed model of translation termination involving intersubunit-, L12-, RF1- and RF3-dynamics.
A class-1 RF recognizes its cognate mRNA stop codon in the ribosome and binds in the A site. Here, the class-1 RF mediates release of the nascent protein attached to the P-site tRNA. After nascent protein release, RF3•GDP is recruited to the ribosome. RF3•GDP is in its closed form and does not form a stable complex with the ribosome; it is possible that initital contact between the ribosome and RF3•GDP is mediated by L12-CTD. As RF3 lodges onto the ribosome, GDP is released and apo-RF3 assumes its semi-open conformation. At this point, apo-RF3 is in contact with L12-CTD, the class-1 RF and 30S protein S12. Upon recruitment of GTP to apo-RF3, RF3•GTP assumes its open conformation and the ribosome changes from the unrotated macrostate I to the rotated macrostate II and the class-1 RF leaves the complex. In this state, RF3•GTP is in contact with L6/SRL and L12-CTD, already interacting with RF3, forms a bridge to L11-NTD. This binding state of RF3•GTP marks the onset of RF3’s GTPase activity leading to cleavage of GTP and release of Pi. RF3•GDP dissociates from the ribosomal complex in its closed conformation and the ribosome is ready for subunit recycling.