Proteome-wide analysis of phospho-regulated PDZ domain interactions

Research output: Contribution to journalArticlepeer-review

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Proteome-wide analysis of phospho-regulated PDZ domain interactions. / Sundell, Gustav N; Arnold, Roland; Ali, Muhammad; Naksukpaiboon, Piangfan; Orts, Julien; Güntert, Peter; Chi, Celestine N; Ivarsson, Ylva.

In: Molecular Systems Biology, Vol. 14, No. 8, 20.08.2018, p. e8129.

Research output: Contribution to journalArticlepeer-review

Harvard

Sundell, GN, Arnold, R, Ali, M, Naksukpaiboon, P, Orts, J, Güntert, P, Chi, CN & Ivarsson, Y 2018, 'Proteome-wide analysis of phospho-regulated PDZ domain interactions', Molecular Systems Biology, vol. 14, no. 8, pp. e8129. https://doi.org/10.15252/msb.20178129

APA

Sundell, G. N., Arnold, R., Ali, M., Naksukpaiboon, P., Orts, J., Güntert, P., Chi, C. N., & Ivarsson, Y. (2018). Proteome-wide analysis of phospho-regulated PDZ domain interactions. Molecular Systems Biology, 14(8), e8129. https://doi.org/10.15252/msb.20178129

Vancouver

Author

Sundell, Gustav N ; Arnold, Roland ; Ali, Muhammad ; Naksukpaiboon, Piangfan ; Orts, Julien ; Güntert, Peter ; Chi, Celestine N ; Ivarsson, Ylva. / Proteome-wide analysis of phospho-regulated PDZ domain interactions. In: Molecular Systems Biology. 2018 ; Vol. 14, No. 8. pp. e8129.

Bibtex

@article{2ec06166082d4776a59ee6555c8c5988,
title = "Proteome-wide analysis of phospho-regulated PDZ domain interactions",
abstract = "A key function of reversible protein phosphorylation is to regulate protein-protein interactions, many of which involve short linear motifs (3-12 amino acids). Motif-based interactions are difficult to capture because of their often low-to-moderate affinities. Here, we describe phosphomimetic proteomic peptide-phage display, a powerful method for simultaneously finding motif-based interaction and pinpointing phosphorylation switches. We computationally designed an oligonucleotide library encoding human C-terminal peptides containing known or predicted Ser/Thr phosphosites and phosphomimetic variants thereof. We incorporated these oligonucleotides into a phage library and screened the PDZ (PSD-95/Dlg/ZO-1) domains of Scribble and DLG1 for interactions potentially enabled or disabled by ligand phosphorylation. We identified known and novel binders and characterized selected interactions through microscale thermophoresis, isothermal titration calorimetry, and NMR We uncover site-specific phospho-regulation of PDZ domain interactions, provide a structural framework for how PDZ domains accomplish phosphopeptide binding, and discuss ligand phosphorylation as a switching mechanism of PDZ domain interactions. The approach is readily scalable and can be used to explore the potential phospho-regulation of motif-based interactions on a large scale.",
author = "Sundell, {Gustav N} and Roland Arnold and Muhammad Ali and Piangfan Naksukpaiboon and Julien Orts and Peter G{\"u}ntert and Chi, {Celestine N} and Ylva Ivarsson",
note = "{\textcopyright} 2018 The Authors. Published under the terms of the CC BY 4.0 license.",
year = "2018",
month = aug,
day = "20",
doi = "10.15252/msb.20178129",
language = "English",
volume = "14",
pages = "e8129",
journal = "Molecular Systems Biology",
issn = "1744-4292",
publisher = "Nature Publishing Group",
number = "8",

}

RIS

TY - JOUR

T1 - Proteome-wide analysis of phospho-regulated PDZ domain interactions

AU - Sundell, Gustav N

AU - Arnold, Roland

AU - Ali, Muhammad

AU - Naksukpaiboon, Piangfan

AU - Orts, Julien

AU - Güntert, Peter

AU - Chi, Celestine N

AU - Ivarsson, Ylva

N1 - © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

PY - 2018/8/20

Y1 - 2018/8/20

N2 - A key function of reversible protein phosphorylation is to regulate protein-protein interactions, many of which involve short linear motifs (3-12 amino acids). Motif-based interactions are difficult to capture because of their often low-to-moderate affinities. Here, we describe phosphomimetic proteomic peptide-phage display, a powerful method for simultaneously finding motif-based interaction and pinpointing phosphorylation switches. We computationally designed an oligonucleotide library encoding human C-terminal peptides containing known or predicted Ser/Thr phosphosites and phosphomimetic variants thereof. We incorporated these oligonucleotides into a phage library and screened the PDZ (PSD-95/Dlg/ZO-1) domains of Scribble and DLG1 for interactions potentially enabled or disabled by ligand phosphorylation. We identified known and novel binders and characterized selected interactions through microscale thermophoresis, isothermal titration calorimetry, and NMR We uncover site-specific phospho-regulation of PDZ domain interactions, provide a structural framework for how PDZ domains accomplish phosphopeptide binding, and discuss ligand phosphorylation as a switching mechanism of PDZ domain interactions. The approach is readily scalable and can be used to explore the potential phospho-regulation of motif-based interactions on a large scale.

AB - A key function of reversible protein phosphorylation is to regulate protein-protein interactions, many of which involve short linear motifs (3-12 amino acids). Motif-based interactions are difficult to capture because of their often low-to-moderate affinities. Here, we describe phosphomimetic proteomic peptide-phage display, a powerful method for simultaneously finding motif-based interaction and pinpointing phosphorylation switches. We computationally designed an oligonucleotide library encoding human C-terminal peptides containing known or predicted Ser/Thr phosphosites and phosphomimetic variants thereof. We incorporated these oligonucleotides into a phage library and screened the PDZ (PSD-95/Dlg/ZO-1) domains of Scribble and DLG1 for interactions potentially enabled or disabled by ligand phosphorylation. We identified known and novel binders and characterized selected interactions through microscale thermophoresis, isothermal titration calorimetry, and NMR We uncover site-specific phospho-regulation of PDZ domain interactions, provide a structural framework for how PDZ domains accomplish phosphopeptide binding, and discuss ligand phosphorylation as a switching mechanism of PDZ domain interactions. The approach is readily scalable and can be used to explore the potential phospho-regulation of motif-based interactions on a large scale.

U2 - 10.15252/msb.20178129

DO - 10.15252/msb.20178129

M3 - Article

C2 - 30126976

VL - 14

SP - e8129

JO - Molecular Systems Biology

JF - Molecular Systems Biology

SN - 1744-4292

IS - 8

ER -