Activation loop phosphorylation of a non-RD receptor kinase initiates plant innate immune signaling.
Activation loop phosphorylation of a non-RD receptor kinase initiates plant innate immune signaling.
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DOI：
10.1073/pnas.2108242118
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发表时间：
2021-09-21
影响因子：
11.1
通讯作者：
Zipfel C
中科院分区：
文献类型：
--
作者：
Bender KW;Couto D;Kadota Y;Macho AP;Sklenar J;Derbyshire P;Bjornson M;DeFalco TA;Petriello A;Font Farre M;Schwessinger B;Ntoukakis V;Stransfeld L;Jones AME;Menke FLH;Zipfel C
催化环HxD基元中缺乏精氨酸的蛋白激酶（即非rd激酶）与跨王国的先天免疫信号有关。磷酸化激活植物免疫受体激酶（RKs），但激活的机制细节有限。我们以非rd免疫RK伸长因子TU受体（伸长因子TU RECEPTOR， EFR）为模型，研究了受体胞质结构域在免疫信号传导中的作用，发现EFR的催化活性对于抗菌免疫是不可或缺的。然而，配体诱导的efr介导的信号是通过激活环磷酸化而不是通过受体蛋白激酶结构域的催化活性启动的。我们提出含有非rd激酶的富含亮氨酸的重复受体激酶复合物通过受体细胞质结构域磷酸化依赖的构象变化被激活。受体激酶（RKs）是细胞外感知和调节发育和应激反应的基础。在植物中，富含亮氨酸的重复受体激酶（LRR-RKs）是主要的肽受体，调节对无数内外刺激的反应。LRR-RK细胞质结构域的磷酸化是配体感知后最早的反应之一，受体及其辅助受体之间的相互转磷酸化被认为可以激活受体复合物。最初是基于油菜素内酯受体的特征提出的，但通过植物RK家族的互转磷酸化进行复杂激活的普遍性尚未得到测试。使用LRR-RK伸长因子受体（EFR）作为模型，我们开始了解激活RK复合物的关键步骤。虽然EFR胞质结构域在体外是一种活性蛋白激酶，在体内以配体依赖的方式磷酸化，但催化缺陷的EFR变体在抗菌免疫中具有功能。这些结果揭示了EFR在触发免疫信号方面的非催化作用，并表明相互转磷酸化并不是LRR-RK复合物激活的普遍要求。相反，我们对EFR的分析以及对文献的详细调查表明，具有RD与非RD蛋白激酶结构域的LRR-RKs之间存在差异。基于新发现的调节体内EFR复合物激活状态的磷酸化位点，我们提出含有非rd蛋白激酶的LRR-RK复合物可能受到配体结合受体磷酸化依赖性构象变化的调节，这可能通过变构或通过驱动复合物的负调节因子解离来启动信号传导。
Protein kinases lacking Arg in the catalytic loop HxD motif (i.e., non-RD kinases) are associated with innate immune signaling across kingdoms. Phosphorylation activates plant immune receptor kinases (RKs), but the mechanistic details of activation are limited. Using the non-RD immune RK ELONGATION FACTOR TU RECEPTOR (EFR) as a model, we investigated the role of the receptor cytoplasmic domain in immune signaling and found that the catalytic activity of EFR is dispensable for antibacterial immunity. Nevertheless, ligand-induced EFR-mediated signaling is initiated by activation loop phosphorylation, but not via the catalytic activity of the receptor protein kinase domain. We propose that leucine-rich repeat-receptor kinase complexes containing a non-RD kinase are activated through phosphorylation-dependent conformational changes of the receptor cytoplasmic domain. Receptor kinases (RKs) are fundamental for extracellular sensing and regulate development and stress responses across kingdoms. In plants, leucine-rich repeat receptor kinases (LRR-RKs) are primarily peptide receptors that regulate responses to myriad internal and external stimuli. Phosphorylation of LRR-RK cytoplasmic domains is among the earliest responses following ligand perception, and reciprocal transphosphorylation between a receptor and its coreceptor is thought to activate the receptor complex. Originally proposed based on characterization of the brassinosteroid receptor, the prevalence of complex activation via reciprocal transphosphorylation across the plant RK family has not been tested. Using the LRR-RK ELONGATION FACTOR TU RECEPTOR (EFR) as a model, we set out to understand the steps critical for activating RK complexes. While the EFR cytoplasmic domain is an active protein kinase in vitro and is phosphorylated in a ligand-dependent manner in vivo, catalytically deficient EFR variants are functional in antibacterial immunity. These results reveal a noncatalytic role for EFR in triggering immune signaling and indicate that reciprocal transphoshorylation is not a ubiquitous requirement for LRR-RK complex activation. Rather, our analysis of EFR along with a detailed survey of the literature suggests a distinction between LRR-RKs with RD- versus non-RD protein kinase domains. Based on newly identified phosphorylation sites that regulate the activation state of the EFR complex in vivo, we propose that LRR-RK complexes containing a non-RD protein kinase may be regulated by phosphorylation-dependent conformational changes of the ligand-binding receptor, which could initiate signaling either allosterically or through driving the dissociation of negative regulators of the complex.
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影响因子：
5.6
作者：
Dufayard JF;Bettembourg M;Fischer I;Droc G;Guiderdoni E;Périn C;Chantret N;Diévart A
通讯作者：
Diévart A
影响因子：
18
作者：
Bjornson M;Pimprikar P;Nürnberger T;Zipfel C
通讯作者：
Zipfel C
影响因子：
64.8
作者：
Chinchilla, Delphine;Zipfel, Cyril;Boller, Thomas
通讯作者：
Boller, Thomas
影响因子：
11.6
作者：
Gómez-Gómez, L;Bauer, Z;Boller, T
通讯作者：
Boller, T
DOI：
10.1073/pnas.1714972115
发表时间：
2018-03-27
影响因子：
11.1
作者：
Hohmann U;Santiago J;Nicolet J;Olsson V;Spiga FM;Hothorn LA;Butenko MA;Hothorn M
通讯作者：
Hothorn M