25 August 2015
Associate Prof Gao Yong-Gui and research team uncover mechanical insights into translational regulation by BipA
BipA (BPI-inducible protein A) gene is highly conserved among bacterial and chloroplast genomes and has been implicated in regulating a variety of cellular processes including bacterial virulence, symbiosis, various stress responses, resistance to host defenses, swarming motility, biofilm, and capsule formation. BipA is an essential factor for bacterial survival at low temperature, nutrient depletion, and various other stress conditions. First, we determined the crystal structures of isolated BipA in various biologically states (nucleotide bound/free). Furthermore, in collaboration with Asst. Prof. Shashi’s lab, we also determined the structure of BipA as a translational GTPase bound to the ribosome in its active form, using the newly established Cryo-EM facility in NTU. Because no other stress response factor is known to interact with the A-site tRNA in ribosome, our results provide a novel mechanistic insight of translational regulation by BipA. In particular, the structure of BipA bound to ribosome with A- and P-site tRNAs reveals a new intermediate state, which implies a function for BipA in positioning of A-site tRNA or in preventing translocation by EF-G, in response to stress. Our findings also boost ribosome as one of the richest validated targets for antibacterial drug discovery.
Paper is published on PNAS (Proceedings of the National Academy of Sciences of the United States) online on 17 August 2015.