Structure of the Type VI Effector-Immunity Complex (Tae4-Tai4) Provides Novel
Insights into the Inhibition Mechanism of the Effector by Its Immunity Protein |
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Authors: | Heng Zhang Heng Zhang Zeng-Qiang Gao Wen-Jia Wang Guang-Feng Liu Jian-Hua Xu Xiao-Dong Su Yu-Hui Dong |
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Institution: | From the ‡State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, No. 5 Yiheyuan Road, Beijing 100871, China and ;the §Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China |
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Abstract: | The type VI secretion system (T6SS), a multisubunit needle-like apparatus, has recently
been found to play a role in interspecies interactions. The Gram-negative bacteria
harboring T6SS (donor) deliver the effectors into their neighboring cells (recipient) to
kill them. Meanwhile, the cognate immunity proteins were employed to protect the donor
cells against the toxic effectors. Tae4 (type VI
amidase effector 4) and Tai4
(type VI amidase
immunity 4) are newly identified T6SS effector-immunity pairs.
Here, we report the crystal structures of Tae4 from Enterobacter cloacae
and Tae4-Tai4 complexes from both E. cloacae and Salmonella
typhimurium. Tae4 acts as a dl-endopeptidase and displays a typical
N1pC/P60 domain. Unlike Tsi1 (type VI
secretion immunity 1), Tai4 is an
all-helical protein and forms a dimer in solution. The small angle x-ray scattering study
combined with the analytical ultracentrifugation reveal that the Tae4-Tai4 complex is a
compact heterotetramer that consists of a Tai4 dimer and two Tae4 molecules in solution.
Structure-based mutational analysis of the Tae4-Tai4 interface shows that a helix
(α3) of one subunit in dimeric Tai4 plays a major role in binding of Tae4, whereas
a protruding loop (L4) in the other subunit is mainly responsible for inhibiting Tae4
activity. The inhibition process requires collaboration between the Tai4 dimer. These
results reveal a novel and unique inhibition mechanism in effector-immunity pairs and
suggest a new strategy to develop antipathogen drugs. |
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Keywords: | Immunology Microbial Pathogenesis Protein Complexes Protein Structure Toxins Tae4-Tai4 Complex Structure Tai4 Dimerization Effector-Immunity Pair Type VI secretion system (T6SS) |
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