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.
authors.affiliation: Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen N, Denmark.
authors.forename: Katrine
authors.initials: K
authors.lastname: Bugge
authors.affiliation: Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen N, Denmark.
authors.forename: Elena
authors.initials: E
authors.lastname: Papaleo
authors.affiliation: Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen N, Denmark.
authors.forename: Gitte W
authors.initials: GW
authors.lastname: Haxholm
authors.affiliation: Physical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK.
authors.forename: Jonathan T S
authors.initials: JT
authors.lastname: Hopper
authors.affiliation: Physical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, South Parks Road, Oxford OX1 3QZ, UK.
authors.forename: Carol V
authors.initials: CV
authors.lastname: Robinson
authors.affiliation: Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen N, Denmark.
authors.forename: Johan G
authors.initials: JG
authors.lastname: Olsen
authors.affiliation: Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen N, Denmark.
authors.forename: Kresten
authors.identifier: 0000-0002-4750-6039
authors.initials: K
authors.lastname: Lindorff-Larsen
authors.affiliation: Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen N, Denmark.
authors.forename: Birthe B
authors.identifier: 0000-0002-7454-1761
authors.initials: BB
authors.lastname: Kragelund
mesh_terms: D018360:Crystallography, X-Ray / Q000379:methods*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008823:Micelles; D008958:Models, Molecular; D000072756:Protein Conformation, alpha-Helical; D000072417:Protein Domains; D011981:Receptors, Prolactin / Q000737:chemistry* / Q000302:isolation & purification; D053838:Scattering, Small Angle
chemical_list: D008823:Micelles; D011981:Receptors, Prolactin