Molecular basis for the binding and selective dephosphorylation of Na+/H+ exchanger 1 by calcineurin

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Standard

Molecular basis for the binding and selective dephosphorylation of Na+/H+ exchanger 1 by calcineurin. / Hendus-Altenburger, Ruth; Wang, Xinru; Sjøgaard-Frich, Lise M.; Pedraz Cuesta, Elena; Sheftic, Sarah R.; Bendsøe, Anne H.; Page, Rebecca; Kragelund, Birthe B.; Pedersen, Stine F; Peti, Wolfgang.

I: Nature Communications, Bind 10, 3489, 2019.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Hendus-Altenburger, R, Wang, X, Sjøgaard-Frich, LM, Pedraz Cuesta, E, Sheftic, SR, Bendsøe, AH, Page, R, Kragelund, BB, Pedersen, SF & Peti, W 2019, 'Molecular basis for the binding and selective dephosphorylation of Na+/H+ exchanger 1 by calcineurin', Nature Communications, bind 10, 3489. https://doi.org/10.1038/s41467-019-11391-7

APA

Hendus-Altenburger, R., Wang, X., Sjøgaard-Frich, L. M., Pedraz Cuesta, E., Sheftic, S. R., Bendsøe, A. H., Page, R., Kragelund, B. B., Pedersen, S. F., & Peti, W. (2019). Molecular basis for the binding and selective dephosphorylation of Na+/H+ exchanger 1 by calcineurin. Nature Communications, 10, [3489]. https://doi.org/10.1038/s41467-019-11391-7

Vancouver

Hendus-Altenburger R, Wang X, Sjøgaard-Frich LM, Pedraz Cuesta E, Sheftic SR, Bendsøe AH o.a. Molecular basis for the binding and selective dephosphorylation of Na+/H+ exchanger 1 by calcineurin. Nature Communications. 2019;10. 3489. https://doi.org/10.1038/s41467-019-11391-7

Author

Hendus-Altenburger, Ruth ; Wang, Xinru ; Sjøgaard-Frich, Lise M. ; Pedraz Cuesta, Elena ; Sheftic, Sarah R. ; Bendsøe, Anne H. ; Page, Rebecca ; Kragelund, Birthe B. ; Pedersen, Stine F ; Peti, Wolfgang. / Molecular basis for the binding and selective dephosphorylation of Na+/H+ exchanger 1 by calcineurin. I: Nature Communications. 2019 ; Bind 10.

Bibtex

@article{87b3ccef7ad8425d85e04c581a3cbaa6,
title = "Molecular basis for the binding and selective dephosphorylation of Na+/H+ exchanger 1 by calcineurin",
abstract = "Very little is known about how Ser/Thr protein phosphatases specifically recruit and dephosphorylate substrates. Here, we identify how the Na+/H+-exchanger 1 (NHE1), a key regulator of cellular pH homeostasis, is regulated by the Ser/Thr phosphatase calcineurin (CN). NHE1 activity is increased by phosphorylation of NHE1 residue T779, which is specifically dephosphorylated by CN. While it is known that Ser/Thr protein phosphatases prefer pThr over pSer, we show that this preference is not key to this exquisite CN selectivity. Rather a combination of molecular mechanisms, including recognition motifs, dynamic charge-charge interactions and a substrate interaction pocket lead to selective dephosphorylation of pT779. Our data identify T779 as a site regulating NHE1-mediated cellular acid extrusion and provides a molecular understanding of NHE1 substrate selection by CN, specifically, and how phosphatases recruit specific substrates, generally.",
author = "Ruth Hendus-Altenburger and Xinru Wang and Sj{\o}gaard-Frich, {Lise M.} and {Pedraz Cuesta}, Elena and Sheftic, {Sarah R.} and Bends{\o}e, {Anne H.} and Rebecca Page and Kragelund, {Birthe B.} and Pedersen, {Stine F} and Wolfgang Peti",
year = "2019",
doi = "10.1038/s41467-019-11391-7",
language = "English",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Molecular basis for the binding and selective dephosphorylation of Na+/H+ exchanger 1 by calcineurin

AU - Hendus-Altenburger, Ruth

AU - Wang, Xinru

AU - Sjøgaard-Frich, Lise M.

AU - Pedraz Cuesta, Elena

AU - Sheftic, Sarah R.

AU - Bendsøe, Anne H.

AU - Page, Rebecca

AU - Kragelund, Birthe B.

AU - Pedersen, Stine F

AU - Peti, Wolfgang

PY - 2019

Y1 - 2019

N2 - Very little is known about how Ser/Thr protein phosphatases specifically recruit and dephosphorylate substrates. Here, we identify how the Na+/H+-exchanger 1 (NHE1), a key regulator of cellular pH homeostasis, is regulated by the Ser/Thr phosphatase calcineurin (CN). NHE1 activity is increased by phosphorylation of NHE1 residue T779, which is specifically dephosphorylated by CN. While it is known that Ser/Thr protein phosphatases prefer pThr over pSer, we show that this preference is not key to this exquisite CN selectivity. Rather a combination of molecular mechanisms, including recognition motifs, dynamic charge-charge interactions and a substrate interaction pocket lead to selective dephosphorylation of pT779. Our data identify T779 as a site regulating NHE1-mediated cellular acid extrusion and provides a molecular understanding of NHE1 substrate selection by CN, specifically, and how phosphatases recruit specific substrates, generally.

AB - Very little is known about how Ser/Thr protein phosphatases specifically recruit and dephosphorylate substrates. Here, we identify how the Na+/H+-exchanger 1 (NHE1), a key regulator of cellular pH homeostasis, is regulated by the Ser/Thr phosphatase calcineurin (CN). NHE1 activity is increased by phosphorylation of NHE1 residue T779, which is specifically dephosphorylated by CN. While it is known that Ser/Thr protein phosphatases prefer pThr over pSer, we show that this preference is not key to this exquisite CN selectivity. Rather a combination of molecular mechanisms, including recognition motifs, dynamic charge-charge interactions and a substrate interaction pocket lead to selective dephosphorylation of pT779. Our data identify T779 as a site regulating NHE1-mediated cellular acid extrusion and provides a molecular understanding of NHE1 substrate selection by CN, specifically, and how phosphatases recruit specific substrates, generally.

U2 - 10.1038/s41467-019-11391-7

DO - 10.1038/s41467-019-11391-7

M3 - Journal article

C2 - 31375679

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 3489

ER -

ID: 225278886