title: NMR characterization of the interaction of the Salmonella type III secretion system protein SipD and bile salts.
abstract: Salmonella and Shigella bacteria require the type III secretion system (T3SS) to inject virulence proteins into their hosts and initiate infections. The tip proteins SipD and IpaD are critical components of the Salmonella and Shigella T3SS, respectively. Recently, SipD and IpaD have been shown to interact with bile salts, which are enriched in the intestines, and are hypothesized to act as environmental sensors for these enteric pathogens. Bile salts activate the Shigella T3SS but repress the Salmonella T3SS, and the mechanism of this differing response to bile salts is poorly understood. Further, how SipD binds to bile salts is currently unknown. Computer modeling predicted that IpaD binds the bile salt deoxycholate in a cleft formed by the N-terminal domain and the long central coiled coil of IpaD. Here, we used NMR methods to determine which SipD residues are affected by the interaction with the bile salts deoxycholate, chenodeoxycholate, and taurodeoxcholate. The bile salts perturbed nearly the same set of SipD residues; however, the largest chemical shift perturbations occurred away from what was predicted for the bile salt binding site in IpaD. Our NMR results indicate that that bile salt interaction of SipD will be different from what was predicted for IpaD, suggesting a possible mechanism for the differing response of Salmonella and Shigella to bile salts.
authors.affiliation: Department of Molecular Biosciences, The University of Kansas, 1200 Sunnyside Avenue, Lawrence, Kansas 66045, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Bryce A
authors.initials: BA
authors.lastname: Nordhues
authors.forename: Dalian
authors.initials: D
authors.lastname: Zhong
authors.forename: Roberto N
authors.initials: RN
authors.lastname: De Guzman
mesh_terms: D000942:Antigens, Bacterial / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry*; D001647:Bile Acids and Salts / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D012475:Salmonella / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001647:Bile Acids and Salts; D008565:Membrane Proteins; C107188:SspD protein, Salmonella typhimurium
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