Deoxycholate Interacts with IpaD of Shigella flexneri in Inducing the Recruitment of IpaB to the Type III Secretion Apparatus Needle Tip

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Issue Date
2008-05-01Author
Strensrud, Kenneth F.
Adam, Philip R.
La Mar, Cassandra D.
Olive, Andrew J.
Lushington, Gerald H.
Sudharsan, Raghavi
Shelton, Naomi L.
Givens, Richard S.
Picking, Wendy Lynn
Picking, William D.
Publisher
American Society for Biochemistry and Molecular Biology
Type
Article
Article Version
Scholarly/refereed, publisher version
Rights
This research was originally published in Journal of Biological Chemistry. Kenneth F. Stensrud, Philip R. Adam, Cassandra D. La Mar, Andrew J. Olive, Gerald H. Lushington, Raghavi Sudharsan, Naomi L. Shelton, Richard S. Givens, Wendy L. Picking and William D. Picking. Deoxycholate Interacts with IpaD of Shigella flexneri in Inducing the Recruitment of IpaB to the Type III Secretion Apparatus Needle Tip. Journal of Biological Chemistry. 2008; 283, 18646-18654. © the American Society for Biochemistry and Molecular Biology.
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Show full item recordAbstract
Type III secretion (TTS) is an essential virulence function for Shigella flexneri that delivers effector proteins that are responsible for bacterial invasion of intestinal epithelial cells. The Shigella TTS apparatus (TTSA) consists of a basal body that spans the bacterial inner and outer membranes and a needle exposed at the pathogen surface. At the distal end of the needle is a “tip complex” composed of invasion plasmid antigen D (IpaD). IpaD not only regulates TTS, but is required for the recruitment and stable association of the translocator protein IpaB at the TTSA needle tip in the presence of deoxycholate or other bile salts. This phenomenon is not accompanied by induction of TTS or the recruitment of IpaC to the Shigella surface. We now show that IpaD specifically binds fluorescein-labeled deoxycholate and, based on energy transfer measurements and docking simulations, this interaction appears to occur where the N-terminal domain of IpaD meets its central coiled-coil, a region that may also be involved in needle-tip interactions. TTS is initiated as a series of distinct steps and that small molecules present in the bacterial milieu are capable of inducing the first step of TSS through interactions with the needle tip protein IpaD. Furthermore, the amino acids proposed to be important for deoxycholate binding by IpaD appear to have significant roles in regulating tip complex composition and pathogen entry into host cells.
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Citation
Stensrud, K. F., Adam, P. R., La Mar, C. D., Olive, A. J., Lushington, G. H., Sudharsan, R., … Picking, W. D. (2008). Deoxycholate Interacts with IpaD of Shigella flexneri in Inducing the Recruitment of IpaB to the Type III Secretion Apparatus Needle Tip. The Journal of Biological Chemistry, 283(27), 18646–18654. http://doi.org/10.1074/jbc.M802799200
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