A large accessory protein interactome is rewired across environments

To characterize how protein-protein interaction (PPI) networks change, we quantified the relative PPI abundance of 1.6 million protein pairs in the yeast Saccharomyces cerevisiae across nine growth conditions, with replication, for a total of 44 million measurements. Our multi-condition screen identified 13,764 pairwise PPIs, a threefold increase over PPIs identified in one condition. A few ‘immutable’ PPIs are present across all conditions, while most ‘mutable’ PPIs are rarely observed. Immutable PPIs aggregate into highly connected ‘core’ network modules, with most network remodeling occurring within a loosely connected ‘accessory’ module. Mutable PPIs are less likely to co-express, co-localize, and be explained by simple mass action kinetics, and more likely to contain proteins with intrinsically disordered regions, implying that environment-dependent association and binding is critical to cellular adaptation. Our results show that protein interactomes are larger than previously thought and contain highly dynamic regions that reorganize to drive or respond to cellular changes.

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A large accessory protein interactome is rewired across environments

10.1101/2020.05.20.106583 ◽

2020 ◽

Author(s):

Zhimin Liu ◽

Darach Miller ◽

Fangfei Li ◽

Xianan Liu ◽

Sasha Levy

Keyword(s):

Fold Increase ◽

Growth Conditions ◽

Mass Action ◽

Core Network ◽

Mass Action Kinetics ◽

Protein Protein Interaction ◽

Intrinsically Disordered ◽

Intrinsically Disordered Regions ◽

Ppi Networks ◽

Network Modules

SummaryTo characterize how protein-protein interaction (PPI) networks change, we quantified the relative PPI abundance of 1.6 million protein pairs in yeast across 9 growth conditions, with replication, for a total of 44 million measurements. Our multi-condition screen identified 13,764 pairwise PPIs, a 3-fold increase over PPIs identified in one condition. A few “immutable” PPIs are present across all conditions, while most “mutable” PPIs are rarely observed. Immutable PPIs aggregate into highly connected “core” network modules, with most network remodeling occurring within a loosely connected “accessory” module. Mutable PPIs are less likely to co-express, co-localize, and be explained by simple mass action kinetics, and more likely to contain proteins with intrinsically disordered regions, implying that environment-dependent association and binding is critical to cellular adaptation. Our results show that protein interactomes are larger than previously thought and contain highly dynamic regions that reorganize to drive or respond to cellular changes.

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Functional Segments on Intrinsically Disordered Regions in Disease-Related Proteins

Biomolecules ◽

10.3390/biom9030088 ◽

2019 ◽

Vol 9 (3) ◽

pp. 88 ◽

Cited By ~ 6

Author(s):

Hiroto Anbo ◽

Masaya Sato ◽

Atsushi Okoshi ◽

Satoshi Fukuchi

Keyword(s):

Intrinsically Disordered Proteins ◽

Disordered Proteins ◽

Protein Protein Interaction ◽

Intrinsically Disordered ◽

Intrinsically Disordered Regions ◽

Protein Protein Interaction Networks ◽

Digestive System Diseases ◽

To Come ◽

Related Proteins ◽

Disordered Regions

One of the unique characteristics of intrinsically disordered proteins (IPDs) is the existence of functional segments in intrinsically disordered regions (IDRs). A typical function of these segments is binding to partner molecules, such as proteins and DNAs. These segments play important roles in signaling pathways and transcriptional regulation. We conducted bioinformatics analysis to search these functional segments based on IDR predictions and database annotations. We found more than a thousand potential functional IDR segments in disease-related proteins. Large fractions of proteins related to cancers, congenital disorders, digestive system diseases, and reproductive system diseases have these functional IDRs. Some proteins in nervous system diseases have long functional segments in IDRs. The detailed analysis of some of these regions showed that the functional segments are located on experimentally verified IDRs. The proteins with functional IDR segments generally tend to come and go between the cytoplasm and the nucleus. Proteins involved in multiple diseases tend to have more protein-protein interactors, suggesting that hub proteins in the protein-protein interaction networks can have multiple impacts on human diseases.

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Computational investigation for modelling the protein-protein interaction of TasA(28-261) – TapA(33-253): a decisive process in biofilm formation by Bacillus subtilis

10.1101/2020.04.26.062109 ◽

2020 ◽

Author(s):

Nidhi Verma ◽

Shubham Srivastava ◽

Ruchi Malik ◽

Jay Kant Yadav ◽

Pankaj Goyal ◽

...

Keyword(s):

Bacillus Subtilis ◽

Protein Interaction ◽

Biofilm Formation ◽

Structural Features ◽

Protein Docking ◽

Structural Basis ◽

Chronic Infections ◽

Protein Protein Interaction ◽

Intrinsically Disordered ◽

Intrinsically Disordered Regions

AbstractBiofilms have significant role in microbial persistence, antibiotic resistance and chronic infections; consequently, there is a pressing need for development of novel “anti-biofilm strategies”. One of the fundamental mechanisms involved in biofilm formation is protein-protein interactions of ‘amyloid like proteins’ (ALPs) in extracellular matrix. Such interactions could be potential targets for development of novel anti-biofilm strategies; therefore, assessing the structural features of these interactions could be of great scientific value. Characterization of biomolecular interaction with conventional structure biology tools including X-Ray diffraction and Nuclear Magnetic Resonance is technically challenging, expensive and time-consuming. In contrast, modelling such interactions is time-efficient, economical and might provide deeper understanding of structural basis of interactions. Therefore, during the present study, protein-protein interaction of TasA(28-261)–TapA(33-253) (which is a decisive process for biofilm formation by Bacillus subtilis) was modeled using in silico approaches viz., molecular modelling, protein-protein docking and molecular dynamics simulations. Results identified amino-acid residues present within intrinsically disordered regions of both proteins to be critical for interaction. These results were further supported with PCA and FEL analyses. Results presented here represent novel finding and we hypothesize that aa identified during the present study could be targeted for inhibition of biofilm formation by B. subtilis.

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Reading the phosphorylation code: binding of the 14-3-3 protein to multivalent client phosphoproteins

Biochemical Journal ◽

10.1042/bcj20200084 ◽

2020 ◽

Vol 477 (7) ◽

pp. 1219-1225 ◽

Cited By ~ 4

Author(s):

Nikolai N. Sluchanko

Keyword(s):

Protein Function ◽

Intrinsically Disordered Protein ◽

Structural Basis ◽

Major Protein ◽

Post Translational Modifications ◽

Protein Protein Interaction ◽

Intrinsically Disordered ◽

Biochemical Journal ◽

Multiple Binding ◽

And Control

Many major protein–protein interaction networks are maintained by ‘hub’ proteins with multiple binding partners, where interactions are often facilitated by intrinsically disordered protein regions that undergo post-translational modifications, such as phosphorylation. Phosphorylation can directly affect protein function and control recognition by proteins that ‘read’ the phosphorylation code, re-wiring the interactome. The eukaryotic 14-3-3 proteins recognizing multiple phosphoproteins nicely exemplify these concepts. Although recent studies established the biochemical and structural basis for the interaction of the 14-3-3 dimers with several phosphorylated clients, understanding their assembly with partners phosphorylated at multiple sites represents a challenge. Suboptimal sequence context around the phosphorylated residue may reduce binding affinity, resulting in quantitative differences for distinct phosphorylation sites, making hierarchy and priority in their binding rather uncertain. Recently, Stevers et al. [Biochemical Journal (2017) 474: 1273–1287] undertook a remarkable attempt to untangle the mechanism of 14-3-3 dimer binding to leucine-rich repeat kinase 2 (LRRK2) that contains multiple candidate 14-3-3-binding sites and is mutated in Parkinson's disease. By using the protein-peptide binding approach, the authors systematically analyzed affinities for a set of LRRK2 phosphopeptides, alone or in combination, to a 14-3-3 protein and determined crystal structures for 14-3-3 complexes with selected phosphopeptides. This study addresses a long-standing question in the 14-3-3 biology, unearthing a range of important details that are relevant for understanding binding mechanisms of other polyvalent proteins.

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