Nature Structural Biology
7, 808 - 815 (2000)
doi:10.1038/79047
Ternary complex between placental lactogen and the extracellular domain of the prolactin receptorPatricia A. Elkins1, 2, Hans W. Christinger1, Yael Sandowski3, Edna Sakal3, Arieh Gertler3, Abraham M. de Vos1
& Anthony A. Kossiakoff1, 41
Department of Protein Engineering, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA. 2
SmithKline Beecham Pharmaceuticals, 709 Swedeland Rd., P.O. Box 1539, King of Prussia, Pennsylvania 19406-0939, USA. 3
Institute of Biochemistry, Food Science and Nutrition, Faculty of Agriculture, The Hebrew University of Jerusalem, Rehovot 76100, Israel. 4
Department of Biochemistry and Molecular Biology, The University of Chicago, Cummings Life Sciences Center, 920 E. 58th St. Chicago, Illinois 60637, USA.
Correspondence should be addressed to Anthony A. Kossiakoff koss@cummings.uchicago.eduThe structure of the ternary complex between ovine placental lactogen (oPL) and the extracellular domain (ECD) of the rat prolactin receptor (rPRLR) reveals that two rPRLR ECDs bind to opposite sides of oPL with pseudo two-fold symmetry. The two oPL receptor binding sites differ significantly in their topography and electrostatic character. These binding interfaces also involve different hydrogen bonding and hydrophobic packing patterns compared to the structurally related human growth hormone (hGH)−receptor complexes. Additionally, the receptor−receptor interactions are different from those of the hGH−receptor complex. The conformational adaptability of prolactin and growth hormone receptors is evidenced by the changes in local conformations of the receptor binding loops and more global changes induced by shifts in the angular relationships between the N- and C-terminal domains, which allow the receptor to bind to the two topographically distinct sites of oPL.
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