GTPases are a well studied super family of proteins most commonly known for their contributions to cell signaling events. Although much is known about eukaryotic GTPases, little is understood about their prokaryotic counterparts. Studies indicate that most, if not all, members of this family assert their function through interactions with the ribosome. BipA, also known as TypA and YlaG, belongs to the translational family GTPases (trGTPases), and is universally conserved in pathogenic bacteria. BipA exhibits two distinct ribosome binding modes which are differentially modulated by guanine nucleotides. Under normal growth conditions and in the presence of GTP, BipA binds to the 70S ribosome. In contrast, during the stringent response, and during adverse environmental conditions, such as growth at high and low temperature, BipA binds the 30S ribosome. In vitro studies suggest that this association is linked to the alarmone ppGpp. We hypothesize that these two ribosome binding modes are related to the physiological function of this protein.
The x-ray crystal structure of BipA revealed that 4 of its 5 domains are topologically equivalent to EF-G. BipA and EF-G share overlapping ribosome binding sites. We have shown that these proteins are not functionally equivalent, likely due to differences in their unique effector domains. Data presented show that multiple domains in BipA contribute to 70S ribosome binding, with the novel C-terminal effector domain being the dominant determinant. Biochemical analysis indicates that this effector domain together with domains III and IV, modulate long-range allosteric regulation in BipA.
