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Structural basis for type VI secretion effector recognition by a cognate immunity protein
Author(s) -
Li Mo,
Le Trong Isolde,
Carl Mike A,
Larson Eric T,
Chou Seemay,
De Leon Justin A,
Dove Simon L,
Stenkamp Ronald E,
Mougous Joseph
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.977.1
Subject(s) - type vi secretion system , effector , secretion , cytoplasm , biology , microbiology and biotechnology , pseudomonas aeruginosa , immunity , toxin , immune system , genetics , bacteria , biochemistry , virulence , gene
The type VI secretion system (T6SS) has emerged as an important mediator of interbacterial interactions. A T6SS from Pseudomonas aeruginosa targets at least three toxic effectors, t ype VI s ecretion e xported 1–3 (Tse1‐3), to recipient Gram‐negative bacterial cells. Tse2 is a potent cytoplasmic toxin that inhibits target cell proliferation through an unknown mechanism. When translocated into other bacterial cells, the protein provides a fitness advantage for P. aeruginosa . The t ype VI s ecretion i mmunity protein 2 (Tsi2) was found to protect against endogenous and intercellularly‐transferred Tse2. Here we showed that Tse2 delivered by the T6SS efficiently induces stasis, not death of recipient cells. Despite direct interaction of Tsi2 and Tse2 in the cytoplasm, we found Tsi2 is dispensable for targeting the toxin to the secretory apparatus. By mapping the results of genetic screening data onto our 1.0 Å X‐ray crystal structure of Tsi2, we discovered an acidic patch on the Tsi2 surface that mediates Tse2 interaction and immunity. Interestingly, our results indicated that Tsi2 shares structural similarity to the N‐terminal domain of the Vti1p SNARE protein and that these proteins interact with binding partners in a chemically and spatially overlapping motif. Our findings provided the first molecular insights into T6 effector secretion and immunity that distinguish the system from analogous cellular pathways.