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Ternary complex between placental lactogen and the extracellular domain of the prolactin receptor

Nature Structural Biology volume 7, pages 808–815 (2000)Cite this article

Abstract

The 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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Figure 1: The oPL–rPRLR2 ternary complex.
Figure 2: Ribbon diagram of oPL (left) and hGH (right).
Figure 3: Sequence alignment of hGH, hPRL and oPL.
Figure 4: Electrostatic rendering of hGH (left) and oPL (right).
Figure 5: Decrease in solvent accessibility on complex formation.
Figure 6: A 2Fo−Fc Fourier map contoured at 1 σ showing the packing of TrpR 104 and TrpR 169.
Figure 7: Electrostatic rendering and receptor–receptor orientation for rPRLR (R1 and R2) (left) and hGHR (right).
Figure 8: van der Waals packing environment of TrpR 169 at site 2 of hGH–hGHR2 superimposed onto oPL–R2.

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Acknowledgements

We thank the staff at the SSRL and at CHESS for help with beamlines 7-1 and A-1, respectively; M. Randal, C. Eigenbrot, N. Gerber, Y. Muller and C. Wiesmann for help with data collection; and W. Anstine and B. Bernat for help with the figures. Part of this research was supported by the United States–Israel Binational Science Foundation.

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Authors and Affiliations

  1. Department of Protein Engineering, Genentech, Inc, 1 DNA Way, South San Francisco, 94080, California, USA

    Patricia A. Elkins, Hans W. Christinger, Abraham M. de Vos & Anthony A. Kossiakoff

  2. SmithKline Beecham Pharmaceuticals, 709 Swedeland Rd., P.O. Box 1539, King of Prussia, 19406-0939, Pennsylvania, USA

    Patricia A. Elkins

  3. Institute of Biochemistry, Food Science and Nutrition, Faculty of Agriculture, The Hebrew University of Jerusalem, Rehovot, 76100, Israel

    Yael Sandowski, Edna Sakal & Arieh Gertler

  4. Department of Biochemistry and Molecular Biology, The University of Chicago, Cummings Life Sciences Center, 920 E. 58th St, Chicago, 60637, Illinois, USA

    Anthony A. Kossiakoff

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Correspondence to Anthony A. Kossiakoff.

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Elkins, P., Christinger, H., Sandowski, Y. et al. Ternary complex between placental lactogen and the extracellular domain of the prolactin receptor. Nat Struct Mol Biol 7, 808–815 (2000). https://doi.org/10.1038/79047

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