Exploring the functional diversification of the C4 proteins encoded by geminiviruses

探索双生病毒编码的 C4 蛋白的功能多样性

• 批准号: 467696175
• 负责人: Professorin Dr. Rosa Lozano-Durán, Ph.D.
• 金额: --
• 依托单位: Zentrum für Molekularbiologie der Pflanzen (ZMBP)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2021
• 资助国家: 德国
• 起止时间: 2020-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/467696175?language=en
• 关键词: Exploring; functional; diversification; C4; proteins

The C4 protein encoded by geminiviruses is an essential pathogenicity determinant and the most divergent protein in this virus family. We have recently described that C4 from Tomato yellow leaf curl virus (TYLCV) localizes in two distinct subcellular compartments, namely plasma membrane (PM)/plasmodesmata (PD) and chloroplasts. PM-localized C4 can suppress the cell-to-cell movement of RNA interference by targeting two plant receptor-like kinases at PD; chloroplast-localized C4 interferes with the downstream activation of defence, suppressing activation of salicylic acid (SA) biosynthesis upon pathogen perception. Therefore, C4 from TYLCV plays a dual role in the suppression of plant defences, illustrating how subcellular compartmentalization of viral proteins can underlie multifunctionality. Although C4 is essential in all species analyzed to date, the properties and roles of most C4 proteins in this virus family remain to be determined. Among geminiviral proteins, C4 seems to be exceptional: while all other proteins are subjected to negative or purifying selection, C4 seems to be under positive selection; the other positional homologues in the geminiviral genome display common or mostly overlapping subcellular localizations, but C4 from different geminiviruses appears in distinct cellular compartments; and no common, general function has been described for C4 proteins so far. Taken together, these observations lead us to hypothesize that C4 is exploring its potential functional landscape, acquiring novel subcellular targeting and interactors and giving rise to divergent properties and functions in different viral species. Further supporting this idea is the finding that replacement of the C4-coding sequence in a given geminivirus species is sufficient to produce a quantitative increase in virulence, acquisition of independence from a satellite molecule, or breakdown of resistance. In this proposal, we intend to explore the diversity in the C4 proteins encoded by different geminiviruses, in terms of their subcellular localization, virulence functions, interactome, host targets, and developmental alterations caused by their expression in planta, and to gain insight into the molecular mechanisms underlying their role during the infection. We anticipate that relevant host processes/pathways/proteins might emerge as convergently targeted by different C4 proteins through independently evolved strategies.

双病毒编码的C4蛋白是该病毒家族中最具分化性的蛋白，也是重要的致病性决定因素。我们最近描述了番茄黄卷叶病毒（TYLCV）的C4定位于两个不同的亚细胞区室，即质膜(PM)/胞间连丝（PD）和叶绿体。pm定位C4可通过靶向两种植物受体样激酶抑制细胞间RNA干扰运动；叶绿体定位C4干扰下游防御激活，抑制病原体感知时水杨酸（SA）生物合成的激活。因此，来自TYLCV的C4在抑制植物防御中起双重作用，说明了病毒蛋白的亚细胞区隔化如何成为多功能性的基础。尽管C4在迄今分析的所有物种中都是必不可少的，但该病毒家族中大多数C4蛋白的特性和作用仍有待确定。在双病毒蛋白中，C4似乎是例外：当所有其他蛋白都受到负选择或纯化选择时，C4似乎受到正选择；双病毒基因组中的其他位置同源物显示出共同或大部分重叠的亚细胞定位，但来自不同双病毒的C4出现在不同的细胞区室中；到目前为止，还没有描述C4蛋白的普遍功能。综上所述，这些观察结果使我们假设C4正在探索其潜在的功能景观，获得新的亚细胞靶向和相互作用，并在不同的病毒物种中产生不同的特性和功能。进一步支持这一观点的发现是，在给定的双病毒物种中替换c4编码序列足以产生毒力的定量增加，从卫星分子中获得独立性，或抗性的破坏。在本研究中，我们将探索不同双病毒编码的C4蛋白在亚细胞定位、毒力功能、相互作用组、宿主靶点以及它们在植物中表达引起的发育改变等方面的多样性，并深入了解它们在感染过程中作用的分子机制。我们预计相关的宿主过程/途径/蛋白质可能通过独立进化的策略成为不同C4蛋白的会聚靶点。