Prokaryotic ABCF proteins in overcoming ribosomal stalling: mechanisms, evolution, and perspective for applications in Bio-manufacturing

ABCF proteins (ABCFs) are key components of prokaryotic translation systems, resolving ribosomal stalling. These ATPases contain two ATPase domains and interdomain linker, the length and composition of which are key determinants of their function. Antibiotic resistance ABCF (ARE-ABCFs) proteins, counteract ribosome-targeting antibiotics by binding to the E site of the 70S ribosome, promoting drug dissociation. In contrast, housekeeping ABCF proteins, such as YfmR and YkpA in Bacillus subtilis, resolve intrinsic translation challenges without conferring antibiotic resistance. YfmR addresses stalling at proline-rich motifs, while YkpA resolves stalling caused by charged motifs. This review draws on the work of Chadani, Boël, Fega, and our own studies to compare the structural and functional diversity of ABCF proteins across bacterial species. It highlights the key roles of ARD/PtlM domains in defining their specific functions and explores future research directions to further our understanding of ABCF proteins in translation control.