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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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/ncomms11578

Authors


More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Sub department:
Physical & Theoretical Chem
Role:
Author
More by this author
Institution:
University of Oxford
Oxford college:
Exeter College
Role:
Author


Publisher:
Springer Nature
Journal:
Nature Communications More from this journal
Volume:
7
Article number:
11578
Publication date:
2016-01-01
Acceptance date:
2016-04-11
DOI:
ISSN:
2041-1723
Pmid:
27174498


Language:
English
Keywords:
Pubs id:
pubs:623576
UUID:
uuid:107db79c-d845-451d-a4a8-5b9da99c5338
Local pid:
pubs:623576
Source identifiers:
623576
Deposit date:
2017-04-08

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