Model for growth hormone receptor activation based on subunit rotation within a receptor dimer
| العنوان: | Model for growth hormone receptor activation based on subunit rotation within a receptor dimer |
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| المؤلفون: | Julian J. Adams, Rebecca A. Pelekanos, William J. McKinstry, Ruth M. Seeber, Yu Wan, Thea A. Monks, Michael J. Waters, Karin A. Eidne, Michael W. Parker, Richard J. C. Brown, Kathryn Palethorpe |
| المصدر: | Nature Structural & Molecular Biology. 12:814-821 |
| بيانات النشر: | Springer Science and Business Media LLC, 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | Models, Molecular, Rotation, Protein subunit, Molecular Sequence Data, Growth hormone receptor, Crystallography, X-Ray, Models, Biological, Cell Line, Mice, Protein structure, Structural Biology, Cricetinae, Chlorocebus aethiops, Animals, Humans, Amino Acid Sequence, Protein Structure, Quaternary, Receptor, Molecular Biology, Chemistry, Receptors, Somatotropin, Ligand (biochemistry), Protein Subunits, Transmembrane domain, Spectrometry, Fluorescence, Förster resonance energy transfer, Biochemistry, Biophysics, Signal transduction, Dimerization |
| الوصف: | Growth hormone is believed to activate the growth hormone receptor (GHR) by dimerizing two identical receptor subunits, leading to activation of JAK2 kinase associated with the cytoplasmic domain. However, we have reported previously that dimerization alone is insufficient to activate full-length GHR. By comparing the crystal structure of the liganded and unliganded human GHR extracellular domain, we show here that there is no substantial change in its conformation on ligand binding. However, the receptor can be activated by rotation without ligand by inserting a defined number of alanine residues within the transmembrane domain. Fluorescence resonance energy transfer (FRET), bioluminescence resonance energy transfer (BRET) and coimmunoprecipitation studies suggest that receptor subunits undergo specific transmembrane interactions independent of hormone binding. We propose an activation mechanism involving a relative rotation of subunits within a dimeric receptor as a result of asymmetric placement of the receptor-binding sites on the ligand. |
| تدمد: | 1545-9985 1545-9993 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b5a479b1c3edf2538aea66e02b930a0bTest https://doi.org/10.1038/nsmb977Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....b5a479b1c3edf2538aea66e02b930a0b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15459985 15459993 |
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