Coiled-coils in the YopD translocator family: a predicted structure unique to the YopD N-terminus contributes to full virulence of Yersinia pseudotuberculosis.
Pathogenic Yersinia all harbor a virulence plasmid-encoded Ysc-Yop T3SS. In this system, translocator function is performed by the hydrophobic proteins YopB and YopD. With the goal to better understand how YopD orchestrates yop-regulatory control, translocon pore formation and Yop effector translocation, we performed an in silico prediction of coiled-coil motifs in YopD and YopD-like sequences from other bacteria. Of interest was a predicted N-terminal coiled-coil that occurred solely in Yersinia YopD sequences. To investigate if this unique feature was biologically relevant, two in cis point mutations were generated with a view to disrupting this putative structure. Both mutants maintained full T3SS function in vitro in terms of environmental control of Yops synthesis and secretion, effector toxin translocation and evasion of phagocytosis and killing by cultured immune cells. However, these same mutants were attenuated for virulence in a murine oral-infection model. The cause of this tardy disease progression is unclear. However, these data indicate that any structural flaw in this element unique to the N-terminus will subtly compromise an aspect of YopD biology. Sub-optimal T3SSs are then formed that are unable to fortify Yersinia against attack by the host innate and adaptive immune response.
Department of Molecular Biology, Umeå University, SE-901 87 Umeå, Sweden.
Tiago R D
TR
Costa
Ayad A A
AA
Amer
Maria
M
Fällman
Anna
A
Fahlgren
Matthew S
MS
Francis
D000595:Amino Acid Sequence; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000235:genetics; D058947:Bacterial Secretion Systems / Q000235:genetics; D002470:Cell Survival; D003198:Computer Simulation; D004912:Erythrocytes; D005260:Female; D006367:HeLa Cells; D006461:Hemolysis; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D016019:Survival Analysis; D014774:Virulence / Q000235:genetics; D015009:Yersinia Infections / Q000382:microbiology*; D015011:Yersinia pseudotuberculosis / Q000737:chemistry / Q000235:genetics / Q000472:pathogenicity*
D001425:Bacterial Outer Membrane Proteins; D058947:Bacterial Secretion Systems; C078910:YopD protein, Yersinia