Fig. 8: Models for the molecular mechanisms of Api137 and Api88.

a Schematic model describing how the two peptides approach and enter the 50S subunit. The cationic peptides Api137 and Api88 can associate with the negatively charged rRNA of the 70S ribosome. The close-up shows a schematic view of the PET. The PET forms a funnel towards the PTC site and exhibits several solvent-exposed nucleobases at the PET exit and near the PTC. The three binding sites are indicated (1, 2, and 3). b, c Structure-based models for peptide entry into the PET and modes of action. b Api137: Occupation of binding site 2 at the exit pore of the PET by Api137 (or Api88) could still allow nascent polypeptide chains to pass. Api137-mediated release factor-dependent inhibition of translation, as proposed by Florin et al. ¹⁴ Upon release of the nascent chain, Api137 interacts with RF1, which is thereby trapped. c Api88: Upon release of the nascent chain, Api88 adopts multiple conformations within the PET and is unable to interact with RF1. Instead, the binding sites in the PET could interfere with regular translation. Both Api137 and Api88 utilize at least two binding sites, consistent with a “sneak-up” model. d The putative entry region for Api88 within the PET to its third binding site is shown (light orange: Api88 in the second binding site, dark orange: Api88 in the third binding site).