Structural and Functional Analysis of BipA, a Regulator of Virulence in Enteropathogenic Escherichia coli
Abstract
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 smallmore »
- Authors:
-
- Univ. of California, Riverside, CA (United States). Dept. of Biochemistry
- Publication Date:
- Research Org.:
- Univ. of California, Riverside, CA (United States)
- Sponsoring Org.:
- USDOE; National Inst. of Health (NIH) (United States); Univ. of California, Riverside, CA (United States)
- OSTI Identifier:
- 1212947
- Grant/Contract Number:
- AC02-06CH11357; P41 GM103403
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Biological Chemistry
- Additional Journal Information:
- Journal Volume: 290; Journal Issue: 34; Journal ID: ISSN 0021-9258
- Publisher:
- American Society for Biochemistry and Molecular Biology
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; small GTPase; structural biology; structure-function; thermodynamics; translation regulation; translational regulation
Citation Formats
Fan, Haitian, Hahm, Joseph, Diggs, Stephen, Perry, J. Jefferson P., and Blaha, Gregor. Structural and Functional Analysis of BipA, a Regulator of Virulence in Enteropathogenic Escherichia coli. United States: N. p., 2015.
Web. doi:10.1074/jbc.M115.659136.
Fan, Haitian, Hahm, Joseph, Diggs, Stephen, Perry, J. Jefferson P., & Blaha, Gregor. Structural and Functional Analysis of BipA, a Regulator of Virulence in Enteropathogenic Escherichia coli. United States. https://doi.org/10.1074/jbc.M115.659136
Fan, Haitian, Hahm, Joseph, Diggs, Stephen, Perry, J. Jefferson P., and Blaha, Gregor. Fri .
"Structural and Functional Analysis of BipA, a Regulator of Virulence in Enteropathogenic Escherichia coli". United States. https://doi.org/10.1074/jbc.M115.659136. https://www.osti.gov/servlets/purl/1212947.
@article{osti_1212947,
title = {Structural and Functional Analysis of BipA, a Regulator of Virulence in Enteropathogenic Escherichia coli},
author = {Fan, Haitian and Hahm, Joseph and Diggs, Stephen and Perry, J. Jefferson P. and Blaha, Gregor},
abstractNote = {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.},
doi = {10.1074/jbc.M115.659136},
journal = {Journal of Biological Chemistry},
number = 34,
volume = 290,
place = {United States},
year = {Fri Jul 10 00:00:00 EDT 2015},
month = {Fri Jul 10 00:00:00 EDT 2015}
}
Web of Science
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