skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Diverse NADase effector families mediate interbacterial antagonism via the type VI secretion system

Authors:
; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
FOREIGN
OSTI Identifier:
1419886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Biological Chemistry; Journal Volume: 293; Journal Issue: 5
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Tang, Jenny Y., Bullen, Nathan P., Ahmad, Shehryar, and Whitney, John C. Diverse NADase effector families mediate interbacterial antagonism via the type VI secretion system. United States: N. p., 2017. Web. doi:10.1074/jbc.RA117.000178.
Tang, Jenny Y., Bullen, Nathan P., Ahmad, Shehryar, & Whitney, John C. Diverse NADase effector families mediate interbacterial antagonism via the type VI secretion system. United States. doi:10.1074/jbc.RA117.000178.
Tang, Jenny Y., Bullen, Nathan P., Ahmad, Shehryar, and Whitney, John C. 2017. "Diverse NADase effector families mediate interbacterial antagonism via the type VI secretion system". United States. doi:10.1074/jbc.RA117.000178.
@article{osti_1419886,
title = {Diverse NADase effector families mediate interbacterial antagonism via the type VI secretion system},
author = {Tang, Jenny Y. and Bullen, Nathan P. and Ahmad, Shehryar and Whitney, John C.},
abstractNote = {},
doi = {10.1074/jbc.RA117.000178},
journal = {Journal of Biological Chemistry},
number = 5,
volume = 293,
place = {United States},
year = 2017,
month =
}
  • Bacteria hijack eukaryotic cells by injecting virulence effectors into host cytosol with a type III secretion system (T3SS). Effectors are targeted with their cognate chaperones to hexameric T3SS ATPase at the bacterial membrane's cytosolic face. In this issue of the Journal of Bacteriology, Roblin et al. (P. Roblin, F. Dewitte, V. Villeret, E. G. Biondi, and C. Bompard, J Bacteriol 197:688–698, 2015, http://dx.doi.org/10.1128/JB.02294-14) show that the T3SS chaperone SigE of Salmonella can form hexameric rings rather than dimers when bound to its cognate effector, SopB, implying a novel multimeric association for chaperone/effector complexes with their ATPase.
  • VirA, a secreted effector protein from Shigella sp., has been shown to be necessary for its virulence. It was also reported that VirA might be related to papain-like cysteine proteases and cleave {alpha}-tubulin, thus facilitating intracellular spreading. We have now determined the crystal structure of VirA at 3.0 {angstrom} resolution. The shape of the molecule resembles the letter 'V,' with the residues in the N-terminal third of the 45-kDa molecule (some of which are disordered) forming one clearly identifiable domain, and the remainder of the molecule completing the V-like structure. The fold of VirA is unique and does not resemblemore » that of any known protein, including papain, although its N-terminal domain is topologically similar to cysteine protease inhibitors such as stefin B. Analysis of the sequence conservation between VirA and its Escherichia coli homologs EspG and EspG2 did not result in identification of any putative protease-like active site, leaving open a possibility that the biological function of VirA in Shigella virulence may not involve direct proteolytic activity.« less
  • Many pathogenic Gram-negative bacteria use a type III secretion system (T3SS) to deliver effector proteins into the host cell where they reprogram host defenses and facilitate pathogenesis. While it has been determined that the first 20 - 30 N-terminal residues usually contain the ‘secretion signal’ that targets effector proteins for translocation, the molecular basis for recognition of this signal is not understood. Recent machine-learning approaches, such as SVM-based Identification and Evaluation of Virulence Effectors (SIEVE), have improved the ability to identify effector proteins from genomics sequence information. While these methods all suggest that the T3SS secretion signal has a characteristicmore » amino acid composition bias, it is still unclear if the amino acid pattern is important and if there are any unifying structural properties that direct recognition. To address these issues a peptide corresponding to the secretion signal for Salmonella enterica serovar Typhimurium effector SseJ was synthesized (residues 1-30, SseJ) along with scrambled peptides of the same amino acid composition that produced high (SseJ-H) and low (SseJ-L) SIEVE scores. The secretion properties of these three peptides were tested using a secretion signal-CyaA fusion assay and their structures systematically probed using circular dichroism, nuclear magnetic resonance, and ion mobility spectrometry-mass spectrometry. The signal-CyaA fusion assay showed that the native and SseJ-H fusion constructs were secreted into J774 macrophage at similar levels via the SPI-2 secretion pathway while secretion of the SseJ-L fusion construct was substantially retarded, suggesting that the SseJ secretion signal was sequence order dependent. The structural studies showed that the SseJ, SseJ-H, and SseJ-L peptides were intrinsically disordered in aqueous solution with only a small predisposition to adopt nascent helical structure in the presence of the powerful structure stabilizing agent, 1,1,1,3,3,3-hexafluoroisopropanol (HFIP). Intrinsic disorder may be a universal feature of effector secretion signals as analogous conclusions were reached following a similar structural characterization of peptides corresponding to the N-terminal regions of the S. Typhimurium effectors SptP, SopD-2, GtgE, and the Yersinia pestis effector YopH.« less