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

Author

Listed:
  • 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)

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.

Suggested Citation

  • Katrine Bugge & Elena Papaleo & Gitte W. Haxholm & Jonathan T. S. Hopper & Carol V. Robinson & Johan G. Olsen & Kresten Lindorff-Larsen & Birthe B. Kragelund, 2016. "A combined computational and structural model of the full-length human prolactin receptor," Nature Communications, Nature, vol. 7(1), pages 1-11, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11578
    DOI: 10.1038/ncomms11578
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