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

Katrine Bugge, Elena Papaleo, Gitte W. Haxholm, Jonathan T. S. Hopper, Carol V. Robinson, Johan G. Olsen, Kresten Lindorff-Larsen and Birthe B. Kragelund ()
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Katrine Bugge: Structural Biology and NMR Laboratory, University of Copenhagen
Elena Papaleo: Structural Biology and NMR Laboratory, University of Copenhagen
Gitte W. Haxholm: Structural Biology and NMR Laboratory, University of Copenhagen
Jonathan T. S. Hopper: Physical and Theoretical Chemistry Laboratory, University of Oxford
Carol V. Robinson: Physical and Theoretical Chemistry Laboratory, University of Oxford
Johan G. Olsen: Structural Biology and NMR Laboratory, University of Copenhagen
Kresten Lindorff-Larsen: Structural Biology and NMR Laboratory, University of Copenhagen
Birthe B. Kragelund: Structural Biology and NMR Laboratory, University of Copenhagen

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms11578

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