The WSXWS motif in cytokine receptors is a molecular switch involved in receptor activation

The WSXWS motif in cytokine receptors is a molecular switch involved in receptor activation: insight from structures of the prolactin receptor

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

The WSXWS motif in cytokine receptors is a molecular switch involved in receptor activation : insight from structures of the prolactin receptor. / Dagil, Robert; Knudsen, Maiken J.; Olsen, Johan Gotthardt; O'Shea, Charlotte; Franzmann, Magnus; Goffin, Vincent; Teilum, Kaare; Breinholt, Jens; Kragelund, Birthe Brandt.

I: Structure, Bind 20, Nr. 2, 2012, s. 270-282.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Dagil, R, Knudsen, MJ, Olsen, JG, O'Shea, C, Franzmann, M, Goffin, V, Teilum, K, Breinholt, J & Kragelund, BB 2012, 'The WSXWS motif in cytokine receptors is a molecular switch involved in receptor activation: insight from structures of the prolactin receptor', Structure, bind 20, nr. 2, s. 270-282. https://doi.org/10.1016/j.str.2011.12.010

APA

Dagil, R., Knudsen, M. J., Olsen, J. G., O'Shea, C., Franzmann, M., Goffin, V., Teilum, K., Breinholt, J., & Kragelund, B. B. (2012). The WSXWS motif in cytokine receptors is a molecular switch involved in receptor activation: insight from structures of the prolactin receptor. Structure, 20(2), 270-282. https://doi.org/10.1016/j.str.2011.12.010

Vancouver

Dagil R, Knudsen MJ, Olsen JG, O'Shea C, Franzmann M, Goffin V o.a. The WSXWS motif in cytokine receptors is a molecular switch involved in receptor activation: insight from structures of the prolactin receptor. Structure. 2012;20(2):270-282. https://doi.org/10.1016/j.str.2011.12.010

Author

Dagil, Robert ; Knudsen, Maiken J. ; Olsen, Johan Gotthardt ; O'Shea, Charlotte ; Franzmann, Magnus ; Goffin, Vincent ; Teilum, Kaare ; Breinholt, Jens ; Kragelund, Birthe Brandt. / The WSXWS motif in cytokine receptors is a molecular switch involved in receptor activation : insight from structures of the prolactin receptor. I: Structure. 2012 ; Bind 20, Nr. 2. s. 270-282.

Bibtex

@article{c7d41c373bf34e459ac6e029eb7d12e6,

title = "The WSXWS motif in cytokine receptors is a molecular switch involved in receptor activation: insight from structures of the prolactin receptor",

abstract = "The prolactin receptor (PRLR) is activated by binding of prolactin in a 2:1 complex, but the activation mechanism is poorly understood. PRLR has a conserved WSXWS motif generic to cytokine class I receptors. We have determined the nuclear magnetic resonance solution structure of the membrane proximal domain of the human PRLR and find that the tryptophans of the motif adopt a T-stack conformation in the unbound state. By contrast, in the hormone bound state, a Trp/Arg-ladder is formed. The conformational change is hormone-dependent and influences the receptor-receptor dimerization site 3. In the constitutively active, breast cancer-related receptor mutant PRLR(I146L), we observed a stabilization of the dimeric state and a change in the dynamics of the motif. Here we demonstrate a structural link between the WSXWS motif, hormone binding, and receptor dimerization and propose it as a general mechanism for class 1 receptor activation.",

author = "Robert Dagil and Knudsen, {Maiken J.} and Olsen, {Johan Gotthardt} and Charlotte O'Shea and Magnus Franzmann and Vincent Goffin and Kaare Teilum and Jens Breinholt and Kragelund, {Birthe Brandt}",

year = "2012",

doi = "10.1016/j.str.2011.12.010",

language = "English",

volume = "20",

pages = "270--282",

journal = "Structure",

issn = "0969-2126",

publisher = "Cell Press",

number = "2",

}

RIS

TY - JOUR

T1 - The WSXWS motif in cytokine receptors is a molecular switch involved in receptor activation

T2 - insight from structures of the prolactin receptor

AU - Dagil, Robert

AU - Knudsen, Maiken J.

AU - Olsen, Johan Gotthardt

AU - O'Shea, Charlotte

AU - Franzmann, Magnus

AU - Goffin, Vincent

AU - Teilum, Kaare

AU - Breinholt, Jens

AU - Kragelund, Birthe Brandt

PY - 2012

Y1 - 2012

N2 - The prolactin receptor (PRLR) is activated by binding of prolactin in a 2:1 complex, but the activation mechanism is poorly understood. PRLR has a conserved WSXWS motif generic to cytokine class I receptors. We have determined the nuclear magnetic resonance solution structure of the membrane proximal domain of the human PRLR and find that the tryptophans of the motif adopt a T-stack conformation in the unbound state. By contrast, in the hormone bound state, a Trp/Arg-ladder is formed. The conformational change is hormone-dependent and influences the receptor-receptor dimerization site 3. In the constitutively active, breast cancer-related receptor mutant PRLR(I146L), we observed a stabilization of the dimeric state and a change in the dynamics of the motif. Here we demonstrate a structural link between the WSXWS motif, hormone binding, and receptor dimerization and propose it as a general mechanism for class 1 receptor activation.

AB - The prolactin receptor (PRLR) is activated by binding of prolactin in a 2:1 complex, but the activation mechanism is poorly understood. PRLR has a conserved WSXWS motif generic to cytokine class I receptors. We have determined the nuclear magnetic resonance solution structure of the membrane proximal domain of the human PRLR and find that the tryptophans of the motif adopt a T-stack conformation in the unbound state. By contrast, in the hormone bound state, a Trp/Arg-ladder is formed. The conformational change is hormone-dependent and influences the receptor-receptor dimerization site 3. In the constitutively active, breast cancer-related receptor mutant PRLR(I146L), we observed a stabilization of the dimeric state and a change in the dynamics of the motif. Here we demonstrate a structural link between the WSXWS motif, hormone binding, and receptor dimerization and propose it as a general mechanism for class 1 receptor activation.

U2 - 10.1016/j.str.2011.12.010

DO - 10.1016/j.str.2011.12.010

M3 - Journal article

C2 - 22325776

VL - 20

SP - 270

EP - 282

JO - Structure

JF - Structure

SN - 0969-2126

IS - 2

ER -

ID: 37546877

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