Bac-7, a mammalian PrAMP, blocks the ribosome

Seefeldt, A.C., Graf, M., Nguyen, F., Pérébaskine, N., Arenz, S., Mardirossian, M., Scocchi, M., Wilson, D.N., Innis, C.A. (2016). Structure of the mammalian antimicrobial peptide Bac7(1-16) bound within the exit tunnel of a bacterial ribosome. Nucleic Acids Res. 44, 2429-2438.

PDB entries: 5F8K, 5FDU, 5FDV

We present crystal structures of the Thermus thermophilus 70S ribosome in complex with the first 16 residues of the bovine PrAMP bactenecin-7 (Bac7) (5F8K), as well as the insect-derived PrAMPs pyrrhocoricin (5FDV) and metalnikowin (5FDU). We further show that Bac7 and Onc112 compete with erythromycin to bind to the nascent polypeptide exit tunnel of the ribosome, and that, similar to Onc112, Bac7 allows initiation complex formation but prevents ribosomes from progressing to the elongation phase. Interestingly, Bac7 is also shown to target mammalian ribosomes, which explains why it must be stored as an inactive pro-peptide inside the neutrophils that produce it.