@article{74095ac29a09404782c7fa979db94fd3,
title = "A Bacterial Effector Mimics a Host HSP90 Client to Undermine Immunity",
abstract = "The molecular chaperone HSP90 facilitates the folding of several client proteins, including innate immune receptors and protein kinases. HSP90 is an essential component of plant and animal immunity, yet pathogenic strategies that directly target the chaperone have not been described. Here, we identify the HopBF1 family of bacterial effectors as eukaryotic-specific HSP90 protein kinases. HopBF1 adopts a minimal protein kinase fold that is recognized by HSP90 as a host client. As a result, HopBF1 phosphorylates HSP90 to completely inhibit the chaperone's ATPase activity. We demonstrate that phosphorylation of HSP90 prevents activation of immune receptors that trigger the hypersensitive response in plants. Consequently, HopBF1-dependent phosphorylation of HSP90 is sufficient to induce severe disease symptoms in plants infected with the bacterial pathogen, Pseudomonas syringae. Collectively, our results uncover a family of bacterial effector kinases with toxin-like properties and reveal a previously unrecognized betrayal mechanism by which bacterial pathogens modulate host immunity.",
keywords = "HSP90, HopBF1, Pseudomonas syringae, chaperone, effector, immunity, kinase, phosphorylation",
author = "Lopez, {Victor A.} and Park, {Brenden C.} and Dominika Nowak and Anju Sreelatha and Patrycja Zembek and Jessie Fernandez and Servage, {Kelly A.} and Marcin Gradowski and Jacek Hennig and Tomchick, {Diana R.} and Krzysztof Paw{\l}owski and Magdalena Krzymowska and Tagliabracci, {Vincent S.}",
note = "Funding Information: We thank Drs. Kim Orth, Neal Alto, Melanie Cobb, Greg Taylor, Dor Salomon, and members of the Tagliabracci laboratory for insightful discussions. We also thank Dr. Farid El Kasmi for providing RPM1 constructs. Results shown in this report are derived from work performed at the Argonne National Laboratory, Structural Biology Center at the Advanced Photon Source. The equipment used was sponsored in part by the Centre for Preclinical Research and Technology (CePT), a project co-sponsored by the European Regional Development Fund and the Innovative Economy Programme, The National Cohesion Strategy of Poland. This work was supported by the NIH (R00DK099254 to V.S.T. T32DK007257-37 to A.S. and T32GM008203-29 to V.A.L.), the Welch Foundation (I-1911 toV.S.T), Cancer Prevention Research Institute of Texas (CPRIT) (RP170674 to V.S.T), and the Polish National Science Centre (2014/15/B/NZ1/03359 to K.P. and 2017/25/B/NZ1/01883 to M.K.). V.S.T. is the Michael L. Rosenberg Scholar in Medical Research, CPRIT Scholar (RR150033), and Searle Scholar. V.A.L. B.C.P. J.H. M.K. and V.S.T. designed the experiments. V.A.L. B.C.P. D.N. A.S, P.Z. J.F. D.R.T. and V.S.T. conducted the experiments. K.A.S. performed the mass spectrometry. M.G. and K.P. performed the bioinformatics. V.A.L. B.C.P. and V.S.T wrote the manuscript with input from all authors. The authors declare no competing interests. Funding Information: We thank Drs. Kim Orth, Neal Alto, Melanie Cobb, Greg Taylor, Dor Salomon, and members of the Tagliabracci laboratory for insightful discussions. We also thank Dr. Farid El Kasmi for providing RPM1 constructs. Results shown in this report are derived from work performed at the Argonne National Laboratory, Structural Biology Center at the Advanced Photon Source. The equipment used was sponsored in part by the Centre for Preclinical Research and Technology (CePT), a project co-sponsored by the European Regional Development Fund and the Innovative Economy Programme , The National Cohesion Strategy of Poland . This work was supported by the NIH ( R00DK099254 to V.S.T., T32DK007257-37 to A.S., and T32GM008203-29 to V.A.L.), the Welch Foundation ( I-1911 toV.S.T), Cancer Prevention Research Institute of Texas (CPRIT) ( RP170674 to V.S.T), and the Polish National Science Centre ( 2014/15/B/NZ1/03359 to K.P. and 2017/25/B/NZ1/01883 to M.K.). V.S.T. is the Michael L. Rosenberg Scholar in Medical Research , CPRIT Scholar (RR150033), and Searle Scholar . Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = sep,
day = "19",
doi = "10.1016/j.cell.2019.08.020",
language = "English (US)",
volume = "179",
pages = "205--218.e21",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "1",
}