3d48: Difference between revisions

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'''Crystal structure of a prolactin receptor antagonist bound to the extracellular domain of the prolactin receptor'''

The crystal structure of the complex between a N-terminally truncated G129R human prolactin (PRL) variant and the extracellular domain (ECD) of the human prolactin receptor (PRLR) was determined at 2.5 A resolution by X-ray crystallography. This structure represents the first experimental structure reported for a PRL variant bound to its cognate receptor. The binding of PRL variants to PRLR-ECD was furthermore characterized by the solution state techniques, hydrogen exchange mass spectrometry (HX-MS) and nuclear magnetic resonance (NMR) spectroscopy. Compared to the binding interface derived from mutagenesis studies, the structural data imply that the definition of PRL binding site 1 (BS1) should be extended to include residues situated in the N-terminal part of loop 1 and in the C-terminus. Comparison of the structure of the receptor bound PRL variant with the structure reported for the unbound form of a similar analogue (Jomain et al. J. Biol. Chem. 282 (45), 33118-33131 (2007)) demonstrates that receptor induced changes in the back-bone of the four helix bundle are subtle, whereas large scale rearrangements and structuring occur in the flexible N-terminal part of loop 1. HX-MS data imply that the dynamics of the four-helix bundle in solution generally become stabilized upon receptor interaction at BS1.

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