Systematic identification of phosphorylation-mediated protein interaction switches

Betts, Matthew J.; Wichmann, Oliver; Utz, Mathias; André, Timon; Petsalaki, Evangelia; Mínguez, Pablo; Parca, Luca; Roth, Frederick P.; Gavin, Anne‐Claude; Bork, Peer; Russell, Robert B.

doi:10.1371/journal.pcbi.1005462

Cited by 54 publications

(45 citation statements)

References 74 publications

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“…Our minimalistic approach to predicting regulatory phosphorylation based on available structural information, though simpler than methods employed previously [52][53][54] , was successful at predicting disruptive phosphorylation (Fig. 5).…”

Section: D Phosphoproteome Analysis Provides Insights Into Function mentioning

confidence: 84%

In-depth and 3-Dimensional Exploration of the Budding Yeast Phosphoproteome

Lanz

Yugandhar

Gupta

et al. 2019

Preprint

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Phosphorylation is one of the most dynamic and widespread post-translational modifications regulating virtually every aspect of eukaryotic cell biology. Here we present a comprehensive phosphoproteomic dataset for budding yeast, comprised of over 30,000 high confidence phosphorylation sites identified by mass spectrometry. This single dataset nearly doubles the size of the known phosphoproteome in budding yeast and defines a set of cell cycle-regulated phosphorylation events. With the goal of enhancing the identification of functional phosphorylation events, we performed computational positioning of phosphorylation sites on available 3D protein structures and systematically identified events predicted to regulate protein complex architecture. Results reveal a large number of phosphorylation sites mapping to or near protein interaction interfaces, many of which result in steric or electrostatic "clashes" predicted to disrupt the interaction. Phosphorylation site mutants experimentally validate our predictions and support a role for phosphorylation in negatively regulating protein-protein interactions. With the advancement of Cryo-EM and the increasing number of available structures, our approach should help drive the functional and spatial exploration of the phosphoproteome.

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Section: D Phosphoproteome Analysis Provides Insights Into Function mentioning

confidence: 84%

In-depth and 3-Dimensional Exploration of the Budding Yeast Phosphoproteome

Lanz

Yugandhar

Gupta

et al. 2019

Preprint

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“…Examining PTMs and sequence annotations associated with proteins (as presented in Basic Protocol 2 and 3) can be useful for identifying specific interacting domains or motifs that contain specific PTMs, and therefore have the potential to affect the binding of proteins (Seet et al, 2006;Van Roey et al, 2012 and may be candidates for further statistical network analyses or experimental validation. Furthermore, visualizing the co-location of PTM sites and sequence annotations on a sequence level can also provide clues as to whether the PTM affects the protein allosterically or contribute to protein-protein binding interfaces (Nussinov et al, 2012;Betts et al, 2017;Pang & Wilkins, 2019).…”

Section: Guidelines For Understanding Resultsmentioning

confidence: 99%

Visualizing Post‐Translational Modifications in Protein Interaction Networks Using PTMOracle

Tay

Liang

Wilkins

et al. 2019

CP in Bioinformatics

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Post‐translational modifications (PTMs) of proteins act as key regulators of protein activity, including the regulation of protein‐protein interactions (PPIs). However, exploring functional links between PTMs and PPIs can be difficult. PTMOracle is a Cytoscape app that facilitates the co‐visualization and co‐analysis of PTMs in the context of PPI networks. PTMOracle also allows extensive data to be integrated and co‐analyzed, allowing the role of domains, motifs, and disordered regions to be considered. Here, we describe several PTMOracle protocols investigating complex PTM‐associated relationships and their role in PPIs. This is assisted by OraclePainter for coloring proteins by the modifications present and visualizing these in the context of networks, by OracleTools for cross‐matching PTMs with sequence feature for all nodes in the network, and by OracleResults for exploring specific proteins and visualizing their PTMs in the context of protein sequences. This unit aims to demonstrate how PTMOracle can be used to systematically explore network visualizations and generate testable hypotheses regarding the functional role of PTMs in PPIs, and how the results can be analyzed to better understand the regulatory role of PTMs in PPIs. © 2019 by John Wiley & Sons, Inc.

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“…Phosphorylation is an important molecular mechanism for regulation of PIPs, acting on both channel gating and protein subcellular trafficking (Maurel et al, 2015, for review). Phosphorylation can also interfere with protein-protein interactions (Betts et al, 2017). Four phosphorylation sites have been described in PIP2;1, at Ser121 (loop B), Ser277, Ser280, and Ser283 (C-terminal end) (Di Pietro et al, 2013;Grondin et al, 2015;Prak et al, 2008).…”

Section: Coexpression Of Pip2;1 With Two Different Quantities Of Caspmentioning

confidence: 99%

Regulation of a plant aquaporin by a Casparian strip membrane domain protein‐like

Champeyroux

Bellati

Barberon

et al. 2019

Plant Cell & Environment

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The absorption of soil water by roots allows plants to maintain their water status. At the endodermis, water transport can be affected by initial formation of a Casparian strip and further deposition of suberin lamellas and regulated by the function of aquaporins. Four Casparian strip membrane domain protein‐like (CASPL; CASPL1B1, CASPL1B2, CASPL1D1, and CASPL1D2) were previously shown to interact with PIP2;1. The present work shows that CASPL1B1, CASPL1B2, and CASPL1D2 are exclusively expressed in suberized endodermal cells, suggesting a cell‐specific role in suberization and/or water transport regulation. When compared with wild‐type plants, and by contrast to caspl1b1*caspl1b2 double loss of function, caspl1d1*caspl1d2 double mutants showed, in some control or NaCl stress experiments and not upon abscisic acid (ABA) treatment, a weak enlargement of the continuous suberization zone. None of the mutants showed root hydraulic conductivity (Lpr) phenotype, whether in control, NaCl, or ABA treatment conditions. The data suggest a slight negative role for CASPL1D1 and CASPL1D2 in suberization under control or salt stress conditions, with no major impact on whole root transport functions. At the molecular level, CASPL1B1 was able to physically interact with PIP2;1 and potentially could influence the regulation of aquaporins by acting on their phosphorylated form.

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Systematic identification of phosphorylation-mediated protein interaction switches

Cited by 54 publications

References 74 publications

In-depth and 3-Dimensional Exploration of the Budding Yeast Phosphoproteome

In-depth and 3-Dimensional Exploration of the Budding Yeast Phosphoproteome

Visualizing Post‐Translational Modifications in Protein Interaction Networks Using PTMOracle

Regulation of a plant aquaporin by a Casparian strip membrane domain protein‐like

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