Structural and Functional Analysis of BipA, a Regulator of Virulence in Enteropathogenic Escherichia coli.
The translational GTPase BipA regulates the expression of virulence and pathogenicity factors in several eubacteria. BipA-dependent expression of virulence factors occurs under starvation conditions, such as encountered during infection of a host. Under these conditions, BipA associates with the small ribosomal subunit. BipA also has a second function to promote the efficiency of late steps in biogenesis of large ribosomal subunits at low temperatures, presumably while bound to the ribosome. During starvation, the cellular concentration of stress alarmone guanosine-3', 5'-bis pyrophosphate (ppGpp) is increased. This increase allows ppGpp to bind to BipA and switch its binding specificity from ribosomes to small ribosomal subunits. A conformational change of BipA upon ppGpp binding could explain the ppGpp regulation of the binding specificity of BipA. Here, we present the structures of the full-length BipA from Escherichia coli in apo, GDP-, and ppGpp-bound forms. The crystal structure and small-angle x-ray scattering data of the protein with bound nucleotides, together with a thermodynamic analysis of the binding of GDP and of ppGpp to BipA, indicate that the ppGpp-bound form of BipA adopts the structure of the GDP form. This suggests furthermore, that the switch in binding preference only occurs when both ppGpp and the small ribosomal subunit are present. This molecular mechanism would allow BipA to interact with both the ribosome and the small ribosomal subunit during stress response.
['Fan|Haitian|H|', 'Hahm|Joseph|J|', 'Diggs|Stephen|S|', 'Perry|J Jefferson P|JJP|', 'Blaha|Gregor|G|']
D001059:Apoproteins D018360:Crystallography, X-Ray D054308:Enteropathogenic Escherichia coli D029968:Escherichia coli Proteins D020558:GTP Phosphohydrolases D015870:Gene Expression D006153:Guanosine Diphosphate D007700:Kinetics D008958:Models, Molecular D010750:Phosphoproteins D011485:Protein Binding D017434:Protein Structure, Tertiary D011755:Pyrophosphatases D011994:Recombinant Proteins D054679:Ribosome Subunits, Small D015398:Signal Transduction D013312:Stress, Physiological D013816:Thermodynamics D014774:Virulence
thermodynamics small GTPase structural biology structure-function translation regulation translational regulation