A Bacterial Effector Mimics a Host HSP90 Client to Undermine Immunity

López, Víctor A.; Park, Brenden C.; Nowak, Dominika; Sreelatha, Anju; Zembek, Patrycja; Fernandez, Jessie; Servage, Kelly A.; Gradowski, Marcin; Hennig, Jacek; Tomchick, Diana R.; Pawłowski, Krzysztof; Krzymowska, Magdalena; Tagliabracci, Vincent S.

doi:10.1016/j.cell.2019.08.020

Cited by 62 publications

(59 citation statements)

References 106 publications

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“…The Arabidopsis BOTRYTIS‐INDUCED KINASE 1 (BIK1), a member of RLCK VII‐8 subfamily, is a direct substrate of several PRR complexes (Couto and Zipfel 2016; Rao et al 2018). BIK1 directly associates with FLS2, and the perception of flg22 by FLS2–BAK1 complex leads to the phosphorylation and dissociation of BIK1 from FLS2 to mediate immune signaling (Lu et al 2010; Zhang et al 2010; Schwessinger et al 2011; Lin et al 2014). A molecular mechanism that regulates the release of BIK1 from FLS2 upon flg22 binding has been reported recently.…”

Section: Recent Discoveries Of the Activation Of Immunity Mediated Bymentioning

confidence: 99%

Plant immune signaling: Advancing on two frontiers

Wang

Feng

Zhou

et al. 2020

JIPB

188

144

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Plants have evolved multiple defense strategies to cope with pathogens, among which plant immune signaling that relies on cell-surface localized and intracellular receptors takes fundamental roles. Exciting breakthroughs were made recently on the signaling mechanisms of pattern recognition receptors (PRRs) and intracellular nucleotide-binding site (NBS) and leucine-rich repeat (LRR) domain receptors (NLRs). This review summarizes the current view of PRRs activation, emphasizing the most recent discoveries about PRRs' dynamic regulation and signaling mechanisms directly leading to downstream molecular events including mitogen-activated protein kinase (MAPK) activation and calcium (Ca 2+ ) burst. Plants also have evolved intracellular NLRs to perceive the presence of specific pathogen effectors and trigger more robust immune responses. We also discuss the current understanding of the mechanisms of NLR activation, which has been greatly advanced by recent breakthroughs including structures of the first full-length plant NLR complex, findings of NLR sensor-helper pairs and novel biochemical activity of Toll/interleukin-1 receptor (TIR) domain.

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Section: Recent Discoveries Of the Activation Of Immunity Mediated Bymentioning

confidence: 99%

Plant immune signaling: Advancing on two frontiers

Wang

Feng

Zhou

et al. 2020

JIPB

188

144

View full text Add to dashboard Cite

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“…The crystal structure of a HopBF1 homolog from the human pathogen Ewingella americana has been determined recently (Lopez et al , 2019). The structure exhibits an atypical minimal protein kinase fold (Fig.…”

Section: Domains Motifs and Scaffolds – What Does The Fold Unfold?mentioning

confidence: 99%

Exploring folds, evolution and host interactions: understanding effector structure/function in disease and immunity

2020

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Summary Over the past decade, tremendous progress has been made in plant pathology, broadening our understanding of how pathogens colonize their hosts. To manipulate host cell physiology and subvert plant immune responses, pathogens secrete an array of effector proteins. A co‐evolutionary arms‐race drives the pathogen to constantly reinvent its effector repertoire to undermine plant immunity. In turn, hosts develop novel immune receptors to maintain effector recognition and mount defences. Understanding how effectors promote disease and how they are perceived by the plant's defence network persist as major subjects in the study of plant–pathogen interactions. Here, we focus on recent advances (over roughly the last two years) in understanding structure/function relationships in effectors from bacteria and filamentous plant pathogens. Structure/function studies of bacterial effectors frequently uncover diverse catalytic activities, while structure‐informed similarity searches have enabled cataloguing of filamentous pathogen effectors. We also suggest how such advances have informed the study of plant–pathogen interactions.

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“…Interestingly, mutation of Lys114 completely abolished kinase activity while mutation of Asp227, that forms an ion pair with Lys114, retained more than 50% of activity. This is reminiscent of the hypomorphic E74A ion pair mutant of the bacterial effector kinase HopBF1 (9). Collectively, our results highlight the residues important for IP6 binding and phosphotransfer.…”

Section: Structure Guided Mutagenesis Highlight the Residues Importanmentioning

confidence: 56%

“…Bacterial effector proteins serve as a diverse pool of proteins in which many atypical and novel biological mechanisms can be found (8). HopBF1, for example, is a family of bacterial effector proteins from Pseudomonas syringae that utilize a novel molecular 'mimicry' to phosphorylate host cell Hsp90 to evade the host immune defense during infection (9). Likewise, Legionella pneumophila, a gram-negative intracellular pathogen known to be the causative agent of Legionnaires disease, contains a plethora of effector proteins with exciting biology.…”

Section: Introductionmentioning

confidence: 99%

A Legionella effector kinase is activated by host inositol hexakisphosphate

Sreelatha

Nolan

Park

et al. 2020

Journal of Biological Chemistry

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The transfer of a phosphate from ATP to a protein substrate, a modification known as protein phosphorylation, is catalyzed by protein kinases. Protein kinases play a crucial role in virtually every cellular activity. Recent studies of atypical protein kinases have highlighted the structural similarity of the kinase superfamily despite notable differences in primary amino acid sequence. Here, using a bioinformatics screen, we searched for putative protein kinases in the intracellular bacterial pathogen Legionella pneumophila and identified the type 4 secretion system effector Lpg2603 as a remote member of the protein kinase superfamily. Employing an array of biochemical and structural biology approaches, including in vitro kinase assays and isothermal titration calorimetry, we show that Lpg2603 is an active protein kinase with several atypical structural features. Importantly, we found that the eukaryote-specific host signaling molecule inositol hexakisphosphate (IP6) is required for Lpg2603 kinase activity. Crystal structures of Lpg2603 in the apo-form and when bound to IP6 revealed an active-site rearrangement that allows for ATP binding and catalysis. Our results on the structure and activity of Lpg2603 reveal a unique mode of regulation of a protein kinase, provide the first example of a bacterial kinase that requires IP6 for its activation, and may aid future work on the function of this effector during Legionella pathogenesis.

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A Bacterial Effector Mimics a Host HSP90 Client to Undermine Immunity

Abstract: Highlights d The bacterial effector HopBF1 adopts a minimal protein kinase fold d HopBF1 phosphorylates and inactivates eukaryotic HSP90 d HopBF1 mimics an HSP90 client to achieve specificity d HopBF1 is sufficient to induce disease symptoms in plants

Cited by 62 publications

References 106 publications

Plant immune signaling: Advancing on two frontiers

Plant immune signaling: Advancing on two frontiers

Exploring folds, evolution and host interactions: understanding effector structure/function in disease and immunity

A Legionella effector kinase is activated by host inositol hexakisphosphate

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