Mapping, modeling, and characterization of protein–protein interactions on a proteomic scale

Cafarelli, TM; Desbuleux, Alice; Wang, Y; Choi, Soon Gang; Ridder, David De; Vidal, Marc

doi:10.1016/j.sbi.2017.05.003

Cited by 62 publications

(39 citation statements)

References 70 publications

(76 reference statements)

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“…The overall proteome-scale of these cellular interactions constitutes an “interactome”. Thus, elucidating the physical characteristics and functional interaction properties of an interactome could potentially reveal novel relationships between host proteins, new community structures as well as unique nodes with signaling cascades 6 , 7 . Such structural and functional topological features provide a range of information on individual nodes and edges, distinct modules, and the entire network as a whole 5 , 8 , 9 .…”

Section: Introductionmentioning

confidence: 99%

“…Several proteome-scale interactomes have been generated in both prokaryotes and eukaryotes including human 6 , 15 , and the reference plant Arabidopsis thaliana (hereafter Arabidopsis) 7 , 16 – 18 . These not only mapped the network and module organization of protein interactions onto the overall cellular organization and function but also allowed understanding of genotype-to-phenotype relationships as well as evolution of biological networks and ancestral gene function 19 .…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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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.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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“…Protein–protein interactions (PPIs) play an essential role in the proper functioning of living cells (Perkins et al , ; Cafarelli et al , ). They transmit information between signaling proteins, regulate enzymatic activities of proteins, and control the cellular tasks of molecular machines (Couzens et al , ; Taipale et al , ; Arumughan et al , ).…”

Section: Introductionmentioning

confidence: 99%

Lu TH y: a double‐readout bioluminescence‐based two‐hybrid technology for quantitative mapping of protein–protein interactions in mammalian cells

Trepte

Kruse

Kostova

et al. 2018

Molecular Systems Biology

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Information on protein–protein interactions (PPIs) is of critical importance for studying complex biological systems and developing therapeutic strategies. Here, we present a double‐readout bioluminescence‐based two‐hybrid technology, termed LuTHy, which provides two quantitative scores in one experimental procedure when testing binary interactions. PPIs are first monitored in cells by quantification of bioluminescence resonance energy transfer (BRET) and, following cell lysis, are again quantitatively assessed by luminescence‐based co‐precipitation (LuC). The double‐readout procedure detects interactions with higher sensitivity than traditional single‐readout methods and is broadly applicable, for example, for detecting the effects of small molecules or disease‐causing mutations on PPIs. Applying LuTHy in a focused screen, we identified 42 interactions for the presynaptic chaperone CSPα, causative to adult‐onset neuronal ceroid lipofuscinosis (ANCL), a progressive neurodegenerative disease. Nearly 50% of PPIs were found to be affected when studying the effect of the disease‐causing missense mutations L115R and ∆L116 in CSPα with LuTHy. Our study presents a robust, sensitive research tool with high utility for investigating the molecular mechanisms by which disease‐associated mutations impair protein activity in biological systems.

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“…PPIs regulate a variety of cellular functions, which are central to understanding the functional relationships between proteins [71]. PPIs have been studied from different perspectives: biochemistry, quantum chemistry, molecular dynamics, and signal transduction, among others [72,73], and a multitude of methods have been applied to detect the PPIs [20]. The most conventional methods are yeast two-hybrid screening and affinity purification coupled to mass spectrometry [74].…”

Section: Discussionmentioning

confidence: 99%

Increased talin–vinculin spatial proximities in livers in response to spotted fever group rickettsial and Ebola virus infections

Liu

Xiao

Zhang

et al. 2020

Laboratory Investigation

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Talin and vinculin, both actin-cytoskeleton-related proteins, have been documented to participate in establishing bacterial infections, respectively, as the adapter protein to mediate cytoskeleton-driven dynamics of the plasma membrane. However, little is known regarding the potential role of the talin-vinculin complex during spotted fever group rickettsial and Ebola virus infections, two dreadful infectious diseases in humans. Many functional properties of proteins are determined by their participation in protein-protein complexes, in a temporal and/or spatial manner. To resolve the limitation of application in using mouse primary antibodies on archival, multiple formalin-fixed mouse tissue samples, which were collected from experiments requiring high biocontainment, we developed a practical strategic proximity ligation assay (PLA) capable of employing one primary antibody raised in mouse to probe talin-vinculin spatial proximal complex in mouse tissue. We observed an increase of talin-vinculin spatial proximities in the livers of spotted fever Rickettsia australis or Ebola virusinfected mice when compared with mock mice. Furthermore, using EPAC1-knockout mice, we found that deletion of EPAC1 could suppress the formation of spatial proximal complex of talin-vinculin in rickettsial infections. In addition, we observed increased colocalization between spatial proximity of talin-vinculin and filamentous actin-specific phalloidin staining in single survival mouse from an ordinarily lethal dose of rickettsial or Ebola virus infection. These findings may help to delineate a fresh insight into the mechanisms underlying liver specific pathogenesis during infection with spotted fever rickettsia or Ebola virus in the mouse model.

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Mapping, modeling, and characterization of protein–protein interactions on a proteomic scale

Cited by 62 publications

References 70 publications

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

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

Lu TH y: a double‐readout bioluminescence‐based two‐hybrid technology for quantitative mapping of protein–protein interactions in mammalian cells

Increased talin–vinculin spatial proximities in livers in response to spotted fever group rickettsial and Ebola virus infections

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