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The intracellular distal tail of the Na+/H+ exchanger NHE1 is intrinsically disordered: implications for NHE1 trafficking

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Standard

The intracellular distal tail of the Na+/H+ exchanger NHE1 is intrinsically disordered: implications for NHE1 trafficking. / Nørholm, Ann-Beth; Hendus-Altenburger, Ruth; Bjerre, Gabriel Peder; Kjærgaard, Magnus; Pedersen, Stine F; Kragelund, Birthe Brandt.

I: Biochemistry, Bind 50, Nr. 17, 03.05.2011, s. 3469-80.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Nørholm, A-B, Hendus-Altenburger, R, Bjerre, GP, Kjærgaard, M, Pedersen, SF & Kragelund, BB 2011, 'The intracellular distal tail of the Na+/H+ exchanger NHE1 is intrinsically disordered: implications for NHE1 trafficking', Biochemistry, bind 50, nr. 17, s. 3469-80. https://doi.org/10.1021/bi1019989

APA

Nørholm, A-B., Hendus-Altenburger, R., Bjerre, G. P., Kjærgaard, M., Pedersen, S. F., & Kragelund, B. B. (2011). The intracellular distal tail of the Na+/H+ exchanger NHE1 is intrinsically disordered: implications for NHE1 trafficking. Biochemistry, 50(17), 3469-80. https://doi.org/10.1021/bi1019989

CBE

Nørholm A-B, Hendus-Altenburger R, Bjerre GP, Kjærgaard M, Pedersen SF, Kragelund BB. 2011. The intracellular distal tail of the Na+/H+ exchanger NHE1 is intrinsically disordered: implications for NHE1 trafficking. Biochemistry. 50(17):3469-80. https://doi.org/10.1021/bi1019989

MLA

Vancouver

Nørholm A-B, Hendus-Altenburger R, Bjerre GP, Kjærgaard M, Pedersen SF, Kragelund BB. The intracellular distal tail of the Na+/H+ exchanger NHE1 is intrinsically disordered: implications for NHE1 trafficking. Biochemistry. 2011 maj 3;50(17):3469-80. https://doi.org/10.1021/bi1019989

Author

Nørholm, Ann-Beth ; Hendus-Altenburger, Ruth ; Bjerre, Gabriel Peder ; Kjærgaard, Magnus ; Pedersen, Stine F ; Kragelund, Birthe Brandt. / The intracellular distal tail of the Na+/H+ exchanger NHE1 is intrinsically disordered: implications for NHE1 trafficking. I: Biochemistry. 2011 ; Bind 50, Nr. 17. s. 3469-80.

Bibtex

@article{46509200a3f544c58724df61b48b3283,
title = "The intracellular distal tail of the Na+/H+ exchanger NHE1 is intrinsically disordered: implications for NHE1 trafficking",
abstract = "Intrinsic disorder is important for protein regulation, yet its role in regulation of ion transport proteins is essentially uninvestigated. The ubiquitous plasma membrane carrier protein Na(+)/H(+) Exchanger isoform 1 (NHE1) plays pivotal roles in cellular pH and volume homeostasis, and its dysfunction is implicated in several clinically important diseases. This study shows, for the first time for any carrier protein, that the distal part of the C-terminal intracellular tail (the cdt, residues V686-Q815) from human (h) NHE1 is intrinsically disordered. Further, we experimentally demonstrated the presence of a similar region of intrinsic disorder (ID) in NHE1 from the teleost fish Pleuronectes americanus (paNHE1), and bioinformatic analysis suggested ID to be conserved in the NHE1 family. The sequential variation in structure propensity as determined by NMR, but not the amplitude, was largely conserved between the h- and paNHE1cdt. This suggests that both proteins contain molecular recognition features (MoRFs), i.e., local, transiently formed structures within an ID region. The functional relevance of the most conserved MoRF was investigated by introducing a point mutation that significantly disrupted the putative binding feature. When this mutant NHE1 was expressed in full length NHE1 in AP1 cells, it exhibited impaired trafficking to the plasma membrane. This study demonstrated that the distal regulatory domain of NHE1 is intrinsically disordered yet contains conserved regions of transient structure. We suggest that normal NHE1 function depends on a protein recognition element within the ID region that may be linked to NHE1 trafficking via an acidic ER export motif.",
keywords = "Amino Acid Motifs, Animals, Cation Transport Proteins, Cell Line, Cell Membrane, Computational Biology, Conserved Sequence, Fish Proteins, Flounder, Glycosylation, Humans, Molecular Sequence Data, Mutation, Nuclear Magnetic Resonance, Biomolecular, Protein Structure, Secondary, Protein Transport, Scattering, Small Angle, Sequence Alignment, Sodium-Hydrogen Antiporter, Species Specificity, X-Ray Diffraction",
author = "Ann-Beth N{\o}rholm and Ruth Hendus-Altenburger and Bjerre, {Gabriel Peder} and Magnus Kj{\ae}rgaard and Pedersen, {Stine F} and Kragelund, {Birthe Brandt}",
year = "2011",
month = may,
day = "3",
doi = "10.1021/bi1019989",
language = "English",
volume = "50",
pages = "3469--80",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "ACS Publications",
number = "17",

}

RIS

TY - JOUR

T1 - The intracellular distal tail of the Na+/H+ exchanger NHE1 is intrinsically disordered: implications for NHE1 trafficking

AU - Nørholm, Ann-Beth

AU - Hendus-Altenburger, Ruth

AU - Bjerre, Gabriel Peder

AU - Kjærgaard, Magnus

AU - Pedersen, Stine F

AU - Kragelund, Birthe Brandt

PY - 2011/5/3

Y1 - 2011/5/3

N2 - Intrinsic disorder is important for protein regulation, yet its role in regulation of ion transport proteins is essentially uninvestigated. The ubiquitous plasma membrane carrier protein Na(+)/H(+) Exchanger isoform 1 (NHE1) plays pivotal roles in cellular pH and volume homeostasis, and its dysfunction is implicated in several clinically important diseases. This study shows, for the first time for any carrier protein, that the distal part of the C-terminal intracellular tail (the cdt, residues V686-Q815) from human (h) NHE1 is intrinsically disordered. Further, we experimentally demonstrated the presence of a similar region of intrinsic disorder (ID) in NHE1 from the teleost fish Pleuronectes americanus (paNHE1), and bioinformatic analysis suggested ID to be conserved in the NHE1 family. The sequential variation in structure propensity as determined by NMR, but not the amplitude, was largely conserved between the h- and paNHE1cdt. This suggests that both proteins contain molecular recognition features (MoRFs), i.e., local, transiently formed structures within an ID region. The functional relevance of the most conserved MoRF was investigated by introducing a point mutation that significantly disrupted the putative binding feature. When this mutant NHE1 was expressed in full length NHE1 in AP1 cells, it exhibited impaired trafficking to the plasma membrane. This study demonstrated that the distal regulatory domain of NHE1 is intrinsically disordered yet contains conserved regions of transient structure. We suggest that normal NHE1 function depends on a protein recognition element within the ID region that may be linked to NHE1 trafficking via an acidic ER export motif.

AB - Intrinsic disorder is important for protein regulation, yet its role in regulation of ion transport proteins is essentially uninvestigated. The ubiquitous plasma membrane carrier protein Na(+)/H(+) Exchanger isoform 1 (NHE1) plays pivotal roles in cellular pH and volume homeostasis, and its dysfunction is implicated in several clinically important diseases. This study shows, for the first time for any carrier protein, that the distal part of the C-terminal intracellular tail (the cdt, residues V686-Q815) from human (h) NHE1 is intrinsically disordered. Further, we experimentally demonstrated the presence of a similar region of intrinsic disorder (ID) in NHE1 from the teleost fish Pleuronectes americanus (paNHE1), and bioinformatic analysis suggested ID to be conserved in the NHE1 family. The sequential variation in structure propensity as determined by NMR, but not the amplitude, was largely conserved between the h- and paNHE1cdt. This suggests that both proteins contain molecular recognition features (MoRFs), i.e., local, transiently formed structures within an ID region. The functional relevance of the most conserved MoRF was investigated by introducing a point mutation that significantly disrupted the putative binding feature. When this mutant NHE1 was expressed in full length NHE1 in AP1 cells, it exhibited impaired trafficking to the plasma membrane. This study demonstrated that the distal regulatory domain of NHE1 is intrinsically disordered yet contains conserved regions of transient structure. We suggest that normal NHE1 function depends on a protein recognition element within the ID region that may be linked to NHE1 trafficking via an acidic ER export motif.

KW - Amino Acid Motifs

KW - Animals

KW - Cation Transport Proteins

KW - Cell Line

KW - Cell Membrane

KW - Computational Biology

KW - Conserved Sequence

KW - Fish Proteins

KW - Flounder

KW - Glycosylation

KW - Humans

KW - Molecular Sequence Data

KW - Mutation

KW - Nuclear Magnetic Resonance, Biomolecular

KW - Protein Structure, Secondary

KW - Protein Transport

KW - Scattering, Small Angle

KW - Sequence Alignment

KW - Sodium-Hydrogen Antiporter

KW - Species Specificity

KW - X-Ray Diffraction

U2 - 10.1021/bi1019989

DO - 10.1021/bi1019989

M3 - Journal article

C2 - 21425832

VL - 50

SP - 3469

EP - 3480

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 17

ER -