Deciphering the Structural and Functional Properties of ABC-F ATPases

Background: The adenosine triphosphate (ATP)-binding cassette (ABC) superfamily of proteins belong to the group of ATP hydrolyzing enzymes (ATPases). They are involved in active transport with the help of their trans-membrane domains (TMDs). However, not all ABC ATPases are engaged in the membrane transport, for e.g., ABC-E and ABC-F ATPases lack TMDs, and they don’t participate in the active transport. Interestingly, ABC-F ATPases are associated with ribosome and this family of protein protects ribosome in different living systems. Most importantly, bacterial ABCF ATPases confer resistance against various classes of antibiotics that act on the ribosome during the process of protein synthesis. Main body: Structurally, ABC-F protein carries dual nucleotide binding domain (ABC1 and ABC2), and domains are connected by a flexible linker (P-site tRNA interaction motif). ABC-F docks ribosome on the E site, and binding of ABC-F protein to ribosome triggers conformational changes in 50S ribosome and this conformational change is essential for smooth occurrence of translation. This mechanism of antibiotic resistance is exploited by different pathogenic bacteria as a part of their stress response mechanism. Conclusion: Our in-silico analysis reveals a strong yet dynamic interaction between the Energy-dependent Translational Throttle A (EttA, a member of ABC-F), and L1 ribosomal protein (largest protein found in the large ribosomal subunit), pivotal for the interaction with ribosome. Hence this review is important for understanding the structure-function relationship of the conserved ATPase and the general mechanism of antibiotic resistance in various domains of life.