Structural and Functional Analysis of BipA, a Regulator of Virulence in Enteropathogenic Escherichia coli

Fan, Haitian; Hahm, Joseph; Diggs, Stephen; Perry, J. Jefferson P.; Blaha, Gregor

doi:10.1074/jbc.M115.659136

Structural and Functional Analysis of BipA, a Regulator of Virulence in Enteropathogenic Escherichia coli

Journal Article · Fri Jul 10 04:00:00 EDT 2015 · Journal of Biological Chemistry

DOI:https://doi.org/10.1074/jbc.M115.659136· OSTI ID:1212947

Fan, Haitian ^[1]; Hahm, Joseph ^[1]; Diggs, Stephen ^[1]; Perry, J. Jefferson P. ^[1]; Blaha, Gregor ^[1]

Univ. of California, Riverside, CA (United States). Dept. of Biochemistry

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. Finally, this molecular mechanism would allow BipA to interact with both the ribosome and the small ribosomal subunit during stress response.

View Accepted Manuscript (DOE)

Research Organization:: Univ. of California, Riverside, CA (United States)

Sponsoring Organization:: USDOE; National Inst. of Health (NIH) (United States); Univ. of California, Riverside, CA (United States)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1212947

Journal Information:: Journal of Biological Chemistry, Journal Name: Journal of Biological Chemistry Journal Issue: 34 Vol. 290; ISSN 0021-9258

Publisher:: American Society for Biochemistry and Molecular BiologyCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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59 BASIC BIOLOGICAL SCIENCES
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structural biology
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Structural and Functional Analysis of BipA, a Regulator of Virulence in Enteropathogenic Escherichia coli

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