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.
A Common Structural Motif in the Binding of Virulence Factors to Bacterial Secretion Chaperones
