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PDBsum entry 6hv6
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References listed in PDB file
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Key reference
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Title
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A cysteine protease-Like domain enhances the cytotoxic effects of the photorhabdus asymbiotica toxin patox.
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Authors
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X.Bogdanovic,
S.Schneider,
N.Levanova,
C.Wirth,
C.Trillhaase,
M.Steinemann,
C.Hunte,
K.Aktories,
T.Jank.
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Ref.
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J Biol Chem, 2019,
294,
1035-1044.
[DOI no: ]
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PubMed id
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Abstract
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The nematode mutualistic bacterium Photorhabdus asymbiotica produces a
large virulence-associated multifunctional protein toxin named PaTox. A
glycosyltransferase domain and a deamidase domain of this large toxin function
as effectors that specifically target host Rho GTPases and heterotrimeric G
proteins, respectively. Modification of these intracellular regulators results
in toxicity toward insects and mammalian cells. In this study, we identified a
cysteine protease-like domain spanning PaTox residues 1844-2114
(PaToxP), upstream of these two effector domains and characterized by
three conserved amino acid residues (Cys-1865, His-1955, and Asp-1975). We
determined the crystal structure of the PaToxP C1865A variant by
native single-wavelength anomalous diffraction of sulfur atoms (sulfur-SAD). At
2.0 Å resolution, this structure revealed a catalytic site typical for
papain-like cysteine proteases, comprising a catalytic triad, oxyanion hole, and
typical secondary structural elements. The PaToxP structure had
highest similarity to that of the AvrPphB protease from Pseudomonas
syringae classified as a C58-protease. Furthermore, we observed that
PaToxP shares structural homology also with non-C58-cysteine
proteases, deubiquitinases, and deamidases. Upon delivery into insect larvae,
PaToxP alone without full-length PaTox had no toxic effects. Yet,
PaToxP expression in mammalian cells was toxic and enhanced the
apoptotic phenotype induced by PaTox in HeLa cells. We propose that
PaToxP is a C58-like cysteine protease module that is essential for
full PaTox activity.
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