Cleavage of ribosomal protein L27 by the Prp protease.

is one of the most important human respiratory pathogens worldwide. The increase in antibiotic resistance in and other pathogens is a significant public health concern. The streptococcal 70S ribosome is a prime target for antibiotics. Ribosomal protein L27 reaches into the peptidyl transferase center with its extended N-terminus and may be involved in the translation process. We have shown that L27 in Firmicutes, including staphylococci and streptococci, has an additional 9-12 amino acid N-terminal extension compared to Gram-negative organisms like . The extension is cleaved by a protease called Prp that is absent from organisms that lack the extension. In , Prp and the N-terminal extension of L27 are essential. Here, we have characterized the cleavage of L27 by Prp in . Prp forms dimers that efficiently cleave L27 . An inactive form of Prp (PrpC34S) binds to L27 without cleaving, whereas L27 with a mutation (F12A) of the cleavage site does not bind Prp. Overexpression of PrpC34S is detrimental to growth. Surprisingly, a Δ strain was viable, apparently due to cleavage of L27 by another, unknown protease. Unlike in , a mutant strain lacking the N-terminal extension of L27 was viable, but showed impaired growth. Our study sheds light on a process that could be exploited for novel antibiotics, but emphasizes important differences between streptococci and staphylococci.