Crystal structure of an antagonist mutant of human growth hormone, G120R, in complex with its receptor at 2.9 A resolution.

The Journal of Biological Chemistry
M SundströmG Norstedt

Abstract

Human growth hormone binds two receptor molecules and thereby induces signal transduction through receptor dimerization. At high concentrations, growth hormone acts as an antagonist because of a large difference in affinities at the respective binding sites. This antagonist action can be enhanced further by reducing binding in the low affinity binding site. A growth hormone antagonist mutant Gly-120 --> Arg, has been crystallized with its receptor as a 1:1 complex and the crystal structure determined at 2.9 A resolution. The 1:1 complex is remarkably similar to the native growth hormone-receptor 1:2 complex. A comparison between the two structures reveals only minimal differences in the conformations of the hormone or its receptor in the two complexes, including the angle between the two immunoglobulin-like domains of the receptor. Further, two symmetry-related 1:1 complexes in the crystal form a 2:2 complex with a large solvent inaccessible area between two receptor molecules. In addition, we present here a native human growth hormone-human growth hormone-binding protein 1:2 complex structure at 2.5 A resolution. One important difference between our structure and the previously published crystal structure at 2.8 A is revealed....Continue Reading

References

Dec 20, 1991·Journal of Molecular Biology·M UltschA A Kossiakoff
Mar 1, 1991·Acta Crystallographica. Section A, Foundations of Crystallography·T A JonesM Kjeldgaard
Sep 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·S S Abdel-MeguidL A Bentle
Jan 20, 1995·Science·T Clackson, J A Wells
Jan 1, 1993·Annual Review of Biophysics and Biomolecular Structure·J A Wells, A M de Vos
Apr 21, 1995·The Journal of Biological Chemistry·M T DattaniN J Marshall
Apr 21, 1995·The Journal of Biological Chemistry·T J WoodL A Haldosén
Oct 1, 1994·Protein Science : a Publication of the Protein Society·A A KossiakoffA M De Vos
Apr 1, 1994·Current Opinion in Cell Biology·J A Wells
Jun 1, 1994·Molecular and Cellular Biology·S S WatowichH F Lodish
Jan 9, 1996·Proceedings of the National Academy of Sciences of the United States of America·J A Wells
Mar 22, 1996·The Journal of Biological Chemistry·P A HardingJ J Kopchick
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4

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Citations

May 1, 1997·Protein Science : a Publication of the Protein Society·R J SimpsonL D Ward
May 6, 1998·Protein Science : a Publication of the Protein Society·D K Smith, H R Treutlein
May 6, 2003·Journal of Molecular Biology·Camille KeelerMichael E Hodsdon
May 22, 2002·Protein Science : a Publication of the Protein Society·Anton V FilikovBassil I Dahiyat
Jul 5, 2003·Chemical & Pharmaceutical Bulletin·Youji KuriharaHideaki Umeyama
Jun 10, 2011·PloS One·Dorothea EmigMario Albrecht
Aug 3, 2011·Future Medicinal Chemistry·Arne SchönErnesto Freire
Jul 21, 2014·Nature Chemical Biology·Jason GavenonisJoshua A Kritzer
Apr 24, 2009·Journal of Pharmaceutical Sciences·Songpon DeechongkitBruce A Kerwin
Oct 17, 2012·Chemical Biology & Drug Design·Yingyun LiuErnesto Freire
Sep 5, 2015·Biophysical Journal·Fidan SumbulTurkan Haliloglu
Jun 28, 2015·International Journal of Biological Macromolecules·Bahman KhamenehMohammad Reza Saberi
Aug 22, 2003·Protein Science : a Publication of the Protein Society·Scott T R WalshAnthony A Kossiakoff
Oct 30, 1998·Endocrine Reviews·S L DropS M De Muinck Keizer-Schrama
Jul 15, 2006·Molecular Endocrinology·Samantha L Gadd, Charles V Clevenger
Jul 11, 2020·Journal of Veterinary Diagnostic Investigation : Official Publication of the American Association of Veterinary Laboratory Diagnosticians, Inc·Aki IioTomoki Motegi
Sep 10, 2010·Endocrinology·Thomas V FlintegaardGert Bolt
Jun 13, 2009·Journal of Receptor and Signal Transduction Research·John Fairbanks Langenheim, Wen Yuan Chen
Mar 1, 1997·The Journal of Peptide Research : Official Journal of the American Peptide Society·E StrandbergG Widmalm
Jan 10, 2021·Trends in Biochemical Sciences·Jennifer Michelle Simien, Ellinor Haglund
Mar 29, 2021·The Journal of Biological Chemistry·Reetobrata BasuJohn J Kopchick
Feb 2, 1999·Journal of Molecular Biology·L Lo ConteJ Janin
Sep 10, 2002·Biologicals : Journal of the International Association of Biological Standardization·Mike CauchyMary Alice Hefford

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