A dynamic charge-charge interaction modulates PP2A:B56 substrate recruitment

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A dynamic charge-charge interaction modulates PP2A:B56 substrate recruitment. / Wang, Xinru; Garvanska, Dimitriya H.; Nasa, Isha; Ueki, Yumi; Zhang, Gang; Kettenbach, Arminja N; Peti, Wolfgang; Nilsson, Jakob; Page, Rebecca.

In: eLife, Vol. 9, 2020.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Wang, X, Garvanska, DH, Nasa, I, Ueki, Y, Zhang, G, Kettenbach, AN, Peti, W, Nilsson, J & Page, R 2020, 'A dynamic charge-charge interaction modulates PP2A:B56 substrate recruitment', eLife, vol. 9. https://doi.org/10.7554/eLife.55966

APA

Wang, X., Garvanska, D. H., Nasa, I., Ueki, Y., Zhang, G., Kettenbach, A. N., ... Page, R. (2020). A dynamic charge-charge interaction modulates PP2A:B56 substrate recruitment. eLife, 9. https://doi.org/10.7554/eLife.55966

Vancouver

Wang X, Garvanska DH, Nasa I, Ueki Y, Zhang G, Kettenbach AN et al. A dynamic charge-charge interaction modulates PP2A:B56 substrate recruitment. eLife. 2020;9. https://doi.org/10.7554/eLife.55966

Author

Wang, Xinru ; Garvanska, Dimitriya H. ; Nasa, Isha ; Ueki, Yumi ; Zhang, Gang ; Kettenbach, Arminja N ; Peti, Wolfgang ; Nilsson, Jakob ; Page, Rebecca. / A dynamic charge-charge interaction modulates PP2A:B56 substrate recruitment. In: eLife. 2020 ; Vol. 9.

Bibtex

@article{b5e423fd194040289d8113908fa7e506,
title = "A dynamic charge-charge interaction modulates PP2A:B56 substrate recruitment",
abstract = "The recruitment of substrates by the ser/thr protein phosphatase 2A (PP2A) is poorly understood, limiting our understanding of PP2A-regulated signaling. Recently, the first PP2A:B56 consensus binding motif, LxxIxE, was identified. However, most validated LxxIxE motifs bind PP2A:B56 with micromolar affinities, suggesting that additional motifs exist to enhance PP2A:B56 binding. Here, we report the requirement of a positively charged motif in a subset of PP2A:B56 interactors, including KIF4A, to facilitate B56 binding via dynamic, electrostatic interactions. Using molecular and cellular experiments, we show that a conserved, negatively charged groove on B56 mediates dynamic binding. We also discovered that this positively charged motif, in addition to facilitating KIF4A dephosphorylation, is essential for condensin I binding, a function distinct and exclusive from PP2A-B56 binding. Together, these results reveal how dynamic, charge-charge interactions fine-tune the interactions mediated by specific motifs, providing a new framework for understanding how PP2A regulation drives cellular signaling.",
author = "Xinru Wang and Garvanska, {Dimitriya H.} and Isha Nasa and Yumi Ueki and Gang Zhang and Kettenbach, {Arminja N} and Wolfgang Peti and Jakob Nilsson and Rebecca Page",
year = "2020",
doi = "10.7554/eLife.55966",
language = "English",
volume = "9",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications Ltd.",

}

RIS

TY - JOUR

T1 - A dynamic charge-charge interaction modulates PP2A:B56 substrate recruitment

AU - Wang, Xinru

AU - Garvanska, Dimitriya H.

AU - Nasa, Isha

AU - Ueki, Yumi

AU - Zhang, Gang

AU - Kettenbach, Arminja N

AU - Peti, Wolfgang

AU - Nilsson, Jakob

AU - Page, Rebecca

PY - 2020

Y1 - 2020

N2 - The recruitment of substrates by the ser/thr protein phosphatase 2A (PP2A) is poorly understood, limiting our understanding of PP2A-regulated signaling. Recently, the first PP2A:B56 consensus binding motif, LxxIxE, was identified. However, most validated LxxIxE motifs bind PP2A:B56 with micromolar affinities, suggesting that additional motifs exist to enhance PP2A:B56 binding. Here, we report the requirement of a positively charged motif in a subset of PP2A:B56 interactors, including KIF4A, to facilitate B56 binding via dynamic, electrostatic interactions. Using molecular and cellular experiments, we show that a conserved, negatively charged groove on B56 mediates dynamic binding. We also discovered that this positively charged motif, in addition to facilitating KIF4A dephosphorylation, is essential for condensin I binding, a function distinct and exclusive from PP2A-B56 binding. Together, these results reveal how dynamic, charge-charge interactions fine-tune the interactions mediated by specific motifs, providing a new framework for understanding how PP2A regulation drives cellular signaling.

AB - The recruitment of substrates by the ser/thr protein phosphatase 2A (PP2A) is poorly understood, limiting our understanding of PP2A-regulated signaling. Recently, the first PP2A:B56 consensus binding motif, LxxIxE, was identified. However, most validated LxxIxE motifs bind PP2A:B56 with micromolar affinities, suggesting that additional motifs exist to enhance PP2A:B56 binding. Here, we report the requirement of a positively charged motif in a subset of PP2A:B56 interactors, including KIF4A, to facilitate B56 binding via dynamic, electrostatic interactions. Using molecular and cellular experiments, we show that a conserved, negatively charged groove on B56 mediates dynamic binding. We also discovered that this positively charged motif, in addition to facilitating KIF4A dephosphorylation, is essential for condensin I binding, a function distinct and exclusive from PP2A-B56 binding. Together, these results reveal how dynamic, charge-charge interactions fine-tune the interactions mediated by specific motifs, providing a new framework for understanding how PP2A regulation drives cellular signaling.

U2 - 10.7554/eLife.55966

DO - 10.7554/eLife.55966

M3 - Journal article

C2 - 32195664

VL - 9

JO - eLife

JF - eLife

SN - 2050-084X

ER -

ID: 239473570