Complex biological systems and cellular networks may underlie most genotype to phenotype relationships. Here, we review basic concepts in network biology, discussing different types of interactome networks and the insights that can come from analyzing them. We elaborate on why interactome networks are important to consider in biology, how they can be mapped and integrated with each other, what global properties are starting to emerge from interactome network models, and how these properties may relate to human disease.

Interactome networks and human disease

Nothing is solid about proteins. Governing rules and established laws are constantly broken. As an example, the last decade and a half have witnessed the fall of one of the major paradigms in structural biology. Contrarily to the more than a century-old belief that the unique function of a protein is determined by its unique structure, which, in its turn, is defined by the unique amino acid sequence, many biologically active proteins lack stable tertiary and/or secondary structure either entirely or at their significant parts. Such intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered domains and functional IDP regions (IDPRs) are highly abundant in nature, and many of them are associated with various human diseases. Such disordered proteins and regions are very different from ordered and well-structured proteins and domains at a variety of levels and possess well-recognizable biases in their amino acid compositions and amino acid sequences. A characteristic feature of these proteins is their exceptional structural heterogeneity, where different parts of a given polypeptide chain can be ordered (or disordered) to different degrees. As a result, a typical IDP/IDPR contains a multitude of potentially foldable, partially foldable, differently foldable or not foldable structural segments. This distribution of conformers is constantly changing in time, where a given segment of a protein molecule has different structures at different time points. The distribution is also constantly changing in response to changes in the environment. This mosaic structural organization is crucial for their functions and many IDPs are engaged in biological functions that rely on high conformational flexibility and that are not accessible to proteins with unique and fixed structures. As a result, the functional repertoire of IDPs complements that of ordered proteins, with IDPs/IDPRs being often involved in regulation, signaling and control. This Sprenger Briefs volume is dedicated to IDPs and IDPRs and an attempt is made to compress a massive amount of knowledge and into a digest that aims to be of use to those wishing a fast entry into this promising field of structural biology.

Intrinsically Disordered Proteins

Plants have evolved a powerful immune system to defend against infection by most microbial organisms. However, successful pathogens, such as Pseudomonas syringae, have developed countermeasures and inject virulence proteins into the host plant cell to suppress immunity and cause devastating diseases. Despite intensive research efforts, the molecular targets of bacterial virulence proteins that are important for plant disease development have remained obscure. Here, we show that a conserved P. syringae virulence protein, HopM1, targets an immunity-associated protein, AtMIN7, in Arabidopsis thaliana. HopM1 mediates the destruction of AtMIN7 via the host proteasome. Our results illustrate a strategy by which a bacterial pathogen exploits the host proteasome to subvert host immunity and causes infection in plants.

Supporting Online Material for A Bacterial Virulence Protein Suppresses Host Innate Immunity to Cause Plant Disease

Plants face a combination of different abiotic stresses under field conditions which are lethal to plant growth and production. Simultaneous occurrence of chilling and drought stresses in plants due to the drastic and rapid global climate changes, can alter the morphological, physiological and molecular responses. Both these stresses adversely affect the plant growth and yields due to physical damages, physiological and biochemical disruptions, and molecular changes. In general, the co-occurrence of chilling and drought combination is even worse for crop production rather than an individual stress condition. Plants attain various common and different physiological and molecular protective approaches for tolerance under chilling and drought stresses. Nevertheless, plant responses to a combination of chilling and drought stresses are unique from those to individual stress. In the present review, we summarized the recent evidence on plant responses to chilling and drought stresses on shared as well as unique basis and tried to find a common thread potentially underlying these responses. We addressed the possible cross talk between plant responses to these stresses and discussed the potential management strategies for regulating the mechanisms of plant tolerance to drought and/or chilling stresses. To date, various novel approaches have been tested in minimizing the negative effects of combine stresses. Despite of the main improvements there is still a big room for improvement in combination of drought and chilling tolerance. Thus, future researches particularly using biotechnological and molecular approaches should be carried out to develop genetically engineered plants with enhanced tolerance against these stress factors.

/pdf/chilling-and-drought-stresses-in-crop-plants-implications-3zvxfs5ueg.pdf

Chilling and Drought Stresses in Crop Plants: Implications, Cross Talk, and Potential Management Opportunities

This article is part of the Distinguished Review Article Series in Conceptual and Methodological Breakthroughs in Molecular Plant-Microbe Interactions. Salicylic acid (SA) is a critical plant hormone that regulates numerous aspects of plant growth and development as well as the activation of defenses against biotic and abiotic stress. Here, we present a historical overview of the progress that has been made to date in elucidating the role of SA in signaling plant immune responses. The ability of plants to develop acquired immunity after pathogen infection was first proposed in 1933. However, most of our knowledge about plant immune signaling was generated over the last three decades, following the discovery that SA is an endogenous defense signal. During this timeframe, researchers have identified i) two pathways through which SA can be synthesized, ii) numerous proteins that regulate SA synthesis and metabolism, and iii) some of the signaling components that function downstream of SA, including a large number of SA targets or receptors. In addition, it has become increasingly evident that SA does not signal immune responses by itself but, rather, as part of an intricate network that involves many other plant hormones. Future efforts to develop a comprehensive understanding of SA-mediated immune signaling will therefore need to close knowledge gaps that exist within the SA pathway itself as well as clarify how crosstalk among the different hormone signaling pathways leads to an immune response that is both robust and optimized for maximal efficacy, depending on the identity of the attacking pathogen.

https://apsjournals.apsnet.org/doi/pdf/10.1094/MPMI-03-18-0067-CR

Systemic Acquired Resistance and Salicylic Acid: Past, Present, and Future.

Aquaporins are membrane channel proteins ubiquitously present in all kingdoms of life. Although aquaporins were originally discovered as water channels, their roles in the transport of small neutral solutes, gasses, and metal ions are now well established. Plants contain the largest number and greatest diversity of aquaporin homologs with diverse subcellular localization patterns, gating properties, and solute specificity. The roles of aquaporins in physiological functions throughout plant growth and development are well known. As an integral regulator of plant-water relations, they are presumed to play an important role in plant defense responses against biotic and abiotic stressors. This review highlights involvement of various aquaporin homologs in plant stress responses against a variety of environmental stresses that disturb plant cell osmotic balance and nutrient homeostasis.

The Roles of Aquaporins in Plant Stress Responses.

TCP three-way handshake: linking developmental processes with plant immunity

In all organisms, major biological processes are controlled by complex protein-protein interactions networks (interactomes), yet their structural complexity presents major analytical challenges. Here, we integrate a compendium of over 4300 phenotypes with Arabidopsis interactome (AI-1MAIN). We show that nodes with high connectivity and betweenness are enriched and depleted in conditional and essential phenotypes, respectively. Such nodes are located in the innermost layers of AI-1MAIN and are preferential targets of pathogen effectors. We extend these network-centric analyses to Cell Surface Interactome (CSILRR) and predict its 35 most influential nodes. To determine their biological relevance, we show that these proteins physically interact with pathogen effectors and modulate plant immunity. Overall, our findings contrast with centrality-lethality rule, discover fast information spreading nodes, and highlight the structural properties of pathogen targets in two different interactomes. Finally, this theoretical framework could possibly be applicable to other inter-species interactomes to reveal pathogen contact points.

/pdf/network-biology-discovers-pathogen-contact-points-in-host-mop9irto46.pdf

Network biology discovers pathogen contact points in host protein-protein interactomes.

Lectin receptor-like kinases (LecRLKs), a plant-specific receptor-like kinase (RLK) sub-family, have been recently found to play crucial roles in plant development and responses to abiotic and biotic stresses. In this review, we first describe the classification and structures of Lectin RLKs. Then we focus on the analysis of functions of LecRLKs in various biological processes and discuss the status of LecRLKs from the ligands they recognize, substrate they target, signaling pathways they are involved in, to the overall regulation of growth-defense tradeoffs. LecRLKs and the signaling components they interact with constitute recognition and protection systems at the plant cell surface contributing to the detection of environmental changes monitoring plant fitness.

/pdf/lectin-receptor-like-kinases-the-sensor-and-mediator-at-the-3021ll51ua.pdf

Lectin Receptor-Like Kinases: The Sensor and Mediator at the Plant Cell Surface.

In the absence of specialized mobile immune cells, plants utilize their localized programmed cell death and Systemic Acquired Resistance to defend themselves against pathogen attack. The contribution of a specific Arabidopsis gene to the overall plant immune response can be specifically and quantitatively assessed by assaying the pathogen growth within the infected tissue. For over three decades, the hemibiotrophic bacterium Pseudomonas syringae pv. maculicola ES4326 (Psm ES4326) has been widely applied as the model pathogen to investigate the molecular mechanisms underlying the Arabidopsis immune response. To deliver pathogens into the leaf tissue, multiple inoculation methods have been established, e.g., syringe infiltration, dip inoculation, spray, vacuum infiltration, and flood inoculation. The following protocol describes an optimized syringe infiltration method to deliver virulent Psm ES4326 into leaves of adult soil-grown Arabidopsis plants and accurately screen for enhanced disease susceptibility (EDS) towards this pathogen. In addition, this protocol can be supplemented with multiple pre-treatments to further dissect specific immune defects within different layers of plant defense, including Salicylic Acid (SA)-Triggered Immunity (STI) and MAMP-Triggered Immunity (MTI).

Bacterial Leaf Infiltration Assay for Fine Characterization of Plant Defense Responses using the Arabidopsis thaliana-Pseudomonas syringae Pathosystem.

Yali Sun

Papers

The Roles of Aquaporins in Plant Stress Responses.

TCP three-way handshake: linking developmental processes with plant immunity

Network biology discovers pathogen contact points in host protein-protein interactomes.

Lectin Receptor-Like Kinases: The Sensor and Mediator at the Plant Cell Surface.

Bacterial Leaf Infiltration Assay for Fine Characterization of Plant Defense Responses using the Arabidopsis thaliana-Pseudomonas syringae Pathosystem.