6HV6

Crystal structure of PatoxP, a cysteine protease-like domain of Photorhabdus asymbiotica toxin PaTox

Summary for 6HV6

• Entry DOI: 10.2210/pdb6hv6/pdb
• Descriptor: Toxin PAU_02230, 1,2-ETHANEDIOL, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (4 entities in total)
• Functional Keywords: cystein protease-like, patox toxin, toxin
• Biological source: Photorhabdus asymbiotica subsp. asymbiotica ATCC 43949
• Total number of polymer chains: 1
• Total formula weight: 52893.23

Authors

Bogdanovic, X.,Wirth, C.,Hunte, C. (deposition date: 2018-10-10, release date: 2018-12-05, Last modification date: 2024-06-19)

Primary citation

Bogdanovic, X.,Schneider, S.,Levanova, N.,Wirth, C.,Trillhaase, C.,Steinemann, M.,Hunte, C.,Aktories, K.,Jank, T.
A cysteine protease-like domain enhances the cytotoxic effects of thePhotorhabdus asymbioticatoxin PaTox.
J. Biol. Chem., 294:1035-1044, 2019

PubMed Abstract: The nematode mutualistic bacterium 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 (PaTox), 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 PaTox 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 PaTox structure had highest similarity to that of the AvrPphB protease from classified as a C58-protease. Furthermore, we observed that PaTox shares structural homology also with non-C58-cysteine proteases, deubiquitinases, and deamidases. Upon delivery into insect larvae, PaTox alone without full-length PaTox had no toxic effects. Yet, PaTox expression in mammalian cells was toxic and enhanced the apoptotic phenotype induced by PaTox in HeLa cells. We propose that PaTox is a C58-like cysteine protease module that is essential for full PaTox activity.

PubMed: 30478175
DOI: 10.1074/jbc.RA118.005043

Experimental method

X-RAY DIFFRACTION (2.001 Å)