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Structure of the Potential Virulence Factor from Francisella tularensis Shows Unexpected Presence of the SHS2 Motif and Similarity to Other Bacterial Virulence Factors
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  • Janette Chammas,
  • Mallika Iyer,
  • George Minasov,
  • Ludmilla Shuvalova ,
  • Wayne Anderson,
  • Adam Godzik
Janette Chammas
University of California Riverside College of Natural and Agricultural Sciences
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Mallika Iyer
Sanford Burnham Prebys Medical Discovery Institute
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George Minasov
Northwestern University Feinberg School of Medicine
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Ludmilla Shuvalova
Northwestern University Feinberg School of Medicine
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Wayne Anderson
Northwestern University
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Adam Godzik
University of California Riverside School of Medicine
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Abstract

Pathogenic bacteria attack their host by secreting virulence factors that in various ways interrupt host defenses and damage their cells. Functions of many virulence factors, even from well-studied pathogens, are still unknown. Francisella tularensis is a class A pathogen and a causative agent of tularemia, a disease that is lethal without proper treatment. Here we report the three-dimensional structure and preliminary analysis of the potential virulence factor identified by the transcriptomic analysis of the F. tularensis disease models that is encoded by the FTT_1539 gene. The structure of the FTT_1539 protein contains two sets of three stranded antiparallel beta sheets, with a helix placed between the first and the second beta strand in each sheet. This structural motif, previously seen in virulence factors from other pathogens, was named the SHS2 motif and identified to play a role in protein-protein interactions and small molecule recognition. Sequence and structure analysis identified FTT_1539 as a member of a large family of secreted proteins from a broad range of pathogenic bacteria, such as Helicobacter pylori and Mycobacterium tuberculosis. While the specific function of the proteins from this class is still unknown, their similarity to the H. pylori Tip-α protein that induces TNF-a and other chemokines through NF-kB activation suggests the existence of a common pathogen-host interference mechanism shared by multiple human pathogens.
02 Mar 2021Submitted to PROTEINS: Structure, Function, and Bioinformatics
18 Nov 2021Assigned to Editor
18 Nov 2021Submission Checks Completed
14 Jan 2022Reviewer(s) Assigned
14 Feb 2022Review(s) Completed, Editorial Evaluation Pending
15 Feb 2022Editorial Decision: Revise Major