Shared Molecular Strategies of the Malaria Parasite P. falciparum and the Human Virus HIV-1

Vizoso-Pinto

et al. 2016

Sci Rep

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Although an abundance of bacteriophages exists, little is known about interactions between their proteins and those of their bacterial hosts. Here, we experimentally determined the phage-host interactomes of the phages Dp-1 and Cp-1 and their underlying protein interaction network in the host Streptococcus pneumoniae. We compared our results to the interaction patterns of E. coli phages lambda and T7. Dp-1 and Cp-1 target highly connected host proteins, occupy central network positions, and reach many protein clusters through the interactions of their targets. In turn, lambda and T7 targets cluster to conserved and essential proteins in E. coli, while such patterns were largely absent in S. pneumoniae. Furthermore, targets in E. coli were mutually strongly intertwined, while targets of Dp-1 and Cp-1 were strongly connected through essential and orthologous proteins in their immediate network vicinity. In both phage-host systems, the impact of phages on their protein targets appears to extend from their network neighbors, since proteins that interact with phage targets were located in central network positions, have a strong topologically disruptive effect and touch complexes with high functional heterogeneity. Such observations suggest that the phages, biological impact is accomplished through a surprisingly limited topological reach of their targets.

“…1C ). Similar observations have been previously reported for human host-viral 20 21 as well as host-parasite interactions 22 23 .…”

Section: Resultssupporting

confidence: 90%

Section: Discussionsupporting

confidence: 79%

The interactome of Streptococcus pneumoniae and its bacteriophages show highly specific patterns of interactions among bacteria and their phages

Mariano

Vizoso-Pinto

et al. 2016

Sci Rep

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“…We observed a similar and yet weaker trend for genes required for infection (Fig. 4A), observations that have been reported for human host-virus interactions (17,21), as well as for host-parasite interactions (22,23). Another topological measure that reflects the central placement of targeted proteins is the shortest path between proteins in a protein interaction network.…”

Section: Figsupporting

confidence: 85%

The Protein Interaction Network of Bacteriophage Lambda with Its Host, Escherichia coli

Blasche

Rajagopala

et al. 2013

J Virol

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dAlthough most of the 73 open reading frames (ORFs) in bacteriophage have been investigated intensively, the function of many genes in host-phage interactions remains poorly understood. Using yeast two-hybrid screens of all lambda ORFs for interactions with its host Escherichia coli, we determined a raw data set of 631 host-phage interactions resulting in a set of 62 high-confidence interactions after multiple rounds of retesting. These links suggest novel regulatory interactions between the E. coli transcriptional network and lambda proteins. Targeted host proteins and genes required for lambda infection are enriched among highly connected proteins, suggesting that bacteriophages resemble interaction patterns of human viruses. Lambda tail proteins interact with both bacterial fimbrial proteins and E. coli proteins homologous to other phage proteins. Lambda appears to dramatically differ from other phages, such as T7, because of its unusually large number of modified and processed proteins, which reduces the number of host-virus interactions detectable by yeast twohybrid screens. More than 60 years ago, Esther Lederberg discovered phage lambda (1). Since this seminal discovery, lambda has become a model organism, contributing to our current understanding of the ways genes work and viruses take control of their hosts. However, phage lambda is still far from being completely understood given that the function of several genes in its 48.5-kb genome remain only vaguely defined. For instance, 14 of 73 predicted lambda proteins are still largely uncharacterized (2).Some of the best-characterized aspects of lambda biology are the genetic switch that determines whether a phage lyses the cell or integrates into its host genome as a prophage and the mechanism of transcriptional antitermination (3). Also, lambda continues to provide new insights into its gene regulatory circuits (4, 5), with recent studies of its DNA packaging motor as the vanguard of nanomotor research (6).Key to lambda biology is a detailed understanding of the phage's proteins, including their interactions. We recently analyzed 95 protein-protein interactions (PPIs) between ϳ70 lambda proteins, capturing 16 of 33 previously published interactions (2). Although protein interactions are reasonably well characterized within the virus particle, host-phage interactions remain incompletely known during the replication and recombination stages of the lambda life cycle in the host cell. In addition, the molecular details of virion assembly are still largely mysterious. Altogether, about 30 host-lambda interactions have been discovered in the past 50 years (Table 1).To improve our understanding of lambda PPIs, we have cloned 68 lambda open reading frames (ORFs) (2) and performed screens against a pooled Escherichia coli library using a multivector yeast two-hybrid (Y2H) strategy. Among a total of 631 raw interactions, we found 244 reproducible interactions. Furthermore, we confirmed 162 interactions in an additional round of retesting, allowing us to obtain an o...

“…S5 clearly indicates that MDSet proteins in the combined human interaction network appeared in significantly more protein complexes than non-MDSet proteins (P = 2.6 × 10 −8 , Wilcoxon test), results that also held for yeast protein complexes (P = 4.1 × 10 −5 ). Furthermore, we determined the complex participation coefficient P i of each protein i (19). P i tends toward 1 if i interacts with proteins in the same protein complexes, and vice versa.…”

Section: Significancementioning

confidence: 99%

Controllability in protein interaction networks

Proc. Natl. Acad. Sci. U.S.A.

2014

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204

218

Recently, the focus of network research shifted to network controllability, prompting us to determine proteins that are important for the control of the underlying interaction webs. In particular, we determined minimum dominating sets of proteins (MDSets) in human and yeast protein interaction networks. Such groups of proteins were defined as optimized subsets where each non-MDSet protein can be reached by an interaction from an MDSet protein.Notably, we found that MDSet proteins were enriched with essential, cancer-related, and virus-targeted genes. Their central position allowed MDSet proteins to connect protein complexes and to have a higher impact on network resilience than hub proteins. As for their involvement in regulatory functions, MDSet proteins were enriched with transcription factors and protein kinases and were significantly involved in bottleneck interactions, regulatory links, phosphorylation events, and genetic interactions.