A combined computational and structural model of the full-length human prolactin receptor

Katrine Østergaard Bugge; Elena Papaleo; Gitte Wolfsberg Haxholm; Jonathan T.S. Hopper; Carol V. Robinson; Johan Gotthardt Olsen; Kresten Lindorff-Larsen; Birthe Brandt Kragelund

doi:10.1038/ncomms11578

A combined computational and structural model of the full-length human prolactin receptor

Katrine Østergaard Bugge, Elena Papaleo, Gitte Wolfsberg Haxholm, Jonathan T.S. Hopper, Carol V. Robinson, Johan Gotthardt Olsen, Kresten Lindorff-Larsen, Birthe Brandt Kragelund

Biomolecular Sciences

33 Citations (Scopus)

125 Downloads (Pure)

Abstract

The prolactin receptor is an archetype member of the class I cytokine receptor family, comprising receptors with fundamental functions in biology as well as key drug targets. Structurally, each of these receptors represent an intriguing diversity, providing an exceptionally challenging target for structural biology. Here, we access the molecular architecture of the monomeric human prolactin receptor by combining experimental and computational efforts. We solve the NMR structure of its transmembrane domain in micelles and collect structural data on overlapping fragments of the receptor with small-angle X-ray scattering, native mass spectrometry and NMR spectroscopy. Along with previously published data, these are integrated by molecular modelling to generate a full receptor structure. The result provides the first full view of a class I cytokine receptor, exemplifying the architecture of more than 40 different receptor chains, and reveals that the extracellular domain is merely the tip of a molecular iceberg.

Original language	English
Article number	11578
Journal	Nature Communications
Volume	7
Number of pages	11
ISSN	2041-1723
DOIs	https://doi.org/10.1038/ncomms11578
Publication status	Published - 13 May 2016

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title = "A combined computational and structural model of the full-length human prolactin receptor",

abstract = "The prolactin receptor is an archetype member of the class I cytokine receptor family, comprising receptors with fundamental functions in biology as well as key drug targets. Structurally, each of these receptors represent an intriguing diversity, providing an exceptionally challenging target for structural biology. Here, we access the molecular architecture of the monomeric human prolactin receptor by combining experimental and computational efforts. We solve the NMR structure of its transmembrane domain in micelles and collect structural data on overlapping fragments of the receptor with small-angle X-ray scattering, native mass spectrometry and NMR spectroscopy. Along with previously published data, these are integrated by molecular modelling to generate a full receptor structure. The result provides the first full view of a class I cytokine receptor, exemplifying the architecture of more than 40 different receptor chains, and reveals that the extracellular domain is merely the tip of a molecular iceberg.",

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AU - Bugge, Katrine Østergaard

AU - Papaleo, Elena

AU - Haxholm, Gitte Wolfsberg

AU - Hopper, Jonathan T.S.

AU - Robinson, Carol V.

AU - Olsen, Johan Gotthardt

AU - Lindorff-Larsen, Kresten

AU - Kragelund, Birthe Brandt

PY - 2016/5/13

Y1 - 2016/5/13

N2 - The prolactin receptor is an archetype member of the class I cytokine receptor family, comprising receptors with fundamental functions in biology as well as key drug targets. Structurally, each of these receptors represent an intriguing diversity, providing an exceptionally challenging target for structural biology. Here, we access the molecular architecture of the monomeric human prolactin receptor by combining experimental and computational efforts. We solve the NMR structure of its transmembrane domain in micelles and collect structural data on overlapping fragments of the receptor with small-angle X-ray scattering, native mass spectrometry and NMR spectroscopy. Along with previously published data, these are integrated by molecular modelling to generate a full receptor structure. The result provides the first full view of a class I cytokine receptor, exemplifying the architecture of more than 40 different receptor chains, and reveals that the extracellular domain is merely the tip of a molecular iceberg.

AB - The prolactin receptor is an archetype member of the class I cytokine receptor family, comprising receptors with fundamental functions in biology as well as key drug targets. Structurally, each of these receptors represent an intriguing diversity, providing an exceptionally challenging target for structural biology. Here, we access the molecular architecture of the monomeric human prolactin receptor by combining experimental and computational efforts. We solve the NMR structure of its transmembrane domain in micelles and collect structural data on overlapping fragments of the receptor with small-angle X-ray scattering, native mass spectrometry and NMR spectroscopy. Along with previously published data, these are integrated by molecular modelling to generate a full receptor structure. The result provides the first full view of a class I cytokine receptor, exemplifying the architecture of more than 40 different receptor chains, and reveals that the extracellular domain is merely the tip of a molecular iceberg.

U2 - 10.1038/ncomms11578

DO - 10.1038/ncomms11578

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SN - 2041-1723

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JO - Nature Communications

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A combined computational and structural model of the full-length human prolactin receptor

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