TY - JOUR
T1 - A combined computational and structural model of the full-length human prolactin receptor
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
M3 - Journal article
C2 - 27174498
SN - 2041-1723
VL - 7
JO - Nature Communications
JF - Nature Communications
M1 - 11578
ER -