Pseudomonas syringae effector HopZ3 suppresses the bacterial AvrPto1-tomato PTO immune complex via acetylation.
Pseudomonas syringae effector HopZ3 suppresses the bacterial AvrPto1-tomato PTO immune complex via acetylation.
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DOI：
10.1371/journal.ppat.1010017
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发表时间：
2021-11
期刊：
影响因子：
6.7
通讯作者：
Greenberg JT
中科院分区：
文献类型：
--
作者：
Jeleńska J;Lee J;Manning AJ;Wolfgeher DJ;Ahn Y;Walters-Marrah G;Lopez IE;Garcia L;McClerklin SA;Michelmore RW;Kron SJ;Greenberg JT
植物病原菌假单胞菌分泌多种调节植物防御的效应物。一些效应子由于植物免疫复合物的特异性识别而触发防御，而另一些效应子可以抑制产生的免疫反应。P. pv.的HopZ 3效应子。PsyB 728 a是一种乙酰转移酶，不仅修饰植物免疫复合物的组分，而且修饰激活这些复合物的Psy效应子。在拟南芥中，HopZ 3乙酰化宿主RPM 1复合物和Psy效应子AvrRpm 1和AvrB 3。本研究的重点是HopZ 3在番茄感染过程中的作用。在Psy抗性番茄中，主要的免疫复合物包括PRF和PTO，这是一种识别AvrPto效应子的RIPK家族激酶。HopZ 3通过抑制AvrPto 1 Psy引发的免疫而作为番茄的毒力因子。HopZ 3乙酰化AvrPto 1 Psy和宿主蛋白PTO、SlRIPK和SlRIN 4s。生化重建和定点突变实验表明，乙酰化作用以多种方式抑制番茄中的免疫信号传导。首先，乙酰化破坏了启动免疫反应所需的关键AvrPto 1 Psy-PTO相互作用。在两种蛋白质的结合界面处和结合所需的其他残基处的未修饰残基被乙酰化。其次，乙酰化发生在对AvrPto 1 Psy功能重要但对PTO结合不重要的残基处。最后，乙酰化减少了促进HopZ 3靶点如AvrPto 1 Psy和PTO的免疫诱导活性所需的特异性磷酸化。在某些情况下，乙酰化与磷酸化竞争。HopZ 3介导的乙酰化抑制了SlRIPK的激酶活性及其先前参与PTO信号传导的SlRIN 4底物的磷酸化。因此，HopZ 3破坏了多种免疫成分和触发它们的效应子的功能，导致对感染的易感性增加。最后，质谱用于映射特定的乙酰化残基证实HopZ 3的不寻常的能力，修改组氨酸除了丝氨酸，苏氨酸和赖氨酸残基。通过分泌毒力蛋白（效应物）进入宿主，病原菌劫持宿主细胞过程，促进细菌定植和疾病发展。对于植物病原菌假单胞菌，效应子的协调作用通常介导宿主防御蛋白的修饰以抑制其功能。然而，植物已经进化出在识别效应子诱导的宿主蛋白质修饰后诱导先天免疫的能力。病原体如何规避某些效应物的免疫诱导活性？他们部署更多的效应器来压制这些防御。HopZ 3是一种来自丁香假单胞菌的乙酰转移酶，在植物病原体效应子中是独一无二的，其特征在于迄今为止它不仅能够修饰效应子触发的免疫途径的多个组分，而且还能够修饰触发效应子本身。通过参与细菌效应子AvrPto 1 Psy和番茄激酶PTO的相互作用和激活的残基的直接乙酰化，HopZ 3修饰破坏它们的结合并阻断免疫诱导所必需的磷酸化。此外，HopZ 3乙酰化PTO信号传导途径中的其他可能组分，包括SlRIPK激酶中的活化位点，导致其活性抑制和SlRIN 4的磷酸化降低。我们的研究强调了HopZ 3依赖性乙酰化的免疫复合物和细菌效应子在抑制效应子诱导的免疫中的重要性。
The plant pathogen Pseudomonas syringae secretes multiple effectors that modulate plant defenses. Some effectors trigger defenses due to specific recognition by plant immune complexes, whereas others can suppress the resulting immune responses. The HopZ3 effector of P. syringae pv. syringae B728a (PsyB728a) is an acetyltransferase that modifies not only components of plant immune complexes, but also the Psy effectors that activate these complexes. In Arabidopsis, HopZ3 acetylates the host RPM1 complex and the Psy effectors AvrRpm1 and AvrB3. This study focuses on the role of HopZ3 during tomato infection. In Psy-resistant tomato, the main immune complex includes PRF and PTO, a RIPK-family kinase that recognizes the AvrPto effector. HopZ3 acts as a virulence factor on tomato by suppressing AvrPto1Psy-triggered immunity. HopZ3 acetylates AvrPto1Psy and the host proteins PTO, SlRIPK and SlRIN4s. Biochemical reconstruction and site-directed mutagenesis experiments suggest that acetylation acts in multiple ways to suppress immune signaling in tomato. First, acetylation disrupts the critical AvrPto1Psy-PTO interaction needed to initiate the immune response. Unmodified residues at the binding interface of both proteins and at other residues needed for binding are acetylated. Second, acetylation occurs at residues important for AvrPto1Psy function but not for binding to PTO. Finally, acetylation reduces specific phosphorylations needed for promoting the immune-inducing activity of HopZ3’s targets such as AvrPto1Psy and PTO. In some cases, acetylation competes with phosphorylation. HopZ3-mediated acetylation suppresses the kinase activity of SlRIPK and the phosphorylation of its SlRIN4 substrate previously implicated in PTO-signaling. Thus, HopZ3 disrupts the functions of multiple immune components and the effectors that trigger them, leading to increased susceptibility to infection. Finally, mass spectrometry used to map specific acetylated residues confirmed HopZ3’s unusual capacity to modify histidine in addition to serine, threonine and lysine residues. By secreting virulence proteins (effectors) into their hosts, pathogenic bacteria hijack host cellular processes to promote bacterial colonization and disease development. For the plant pathogen Pseudomonas syringae, the coordinated action of effectors often mediates modifications of host defense proteins to inhibit their function. However, plants have evolved the ability to induce innate immunity upon recognition of effector-induced modifications of host proteins. How do pathogens circumvent the immune-inducing activity of certain effectors? They deploy more effectors to suppress these defenses. HopZ3, an acetyltransferase from P. syringae, is unique among plant pathogen effectors characterized so far in its ability to modify not only multiple components of the effector-triggered immune pathway, but also the triggering effector itself. Through the direct acetylation of residues involved in the interaction and activation of the bacterial effector AvrPto1Psy and tomato kinase PTO, HopZ3 modifications disrupt their binding and block phosphorylations necessary for immune induction. Additionally, HopZ3 acetylates other possible components in the PTO signaling pathway, including activation sites in SlRIPK kinase, leading to suppression of its activity and reduced phosphorylation of SlRIN4s. Our study emphasizes the importance of HopZ3-dependent acetylation of immune complexes and bacterial effectors across plant species in the suppression of effector-induced immunity.
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