scholarly journals A Short Isoform of the Human Growth Hormone Receptor Functions as a Dominant Negative Inhibitor of the Full-Length Receptor and Generates Large Amounts of Binding Protein

1997 ◽  
Vol 11 (3) ◽  
pp. 265-273 ◽  
Author(s):  
R. J. M. Ross ◽  
N. Esposito ◽  
X. Y. Shen ◽  
S. Von Laue ◽  
S. L. Chew ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Human Growth Hormone ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Binding Protein ◽  
Human Growth ◽  
Dominant Negative ◽  
Full Length ◽  
Dominant Negative Inhibitor ◽  
Human Growth Hormone Receptor

scholarly journals Order and disorder—An integrative structure of the full-length human growth hormone receptor

2021 ◽  
Vol 7 (27) ◽  
pp. eabh3805
Author(s):  
Noah Kassem ◽  
Raul Araya-Secchi ◽  
Katrine Bugge ◽  
Abigail Barclay ◽  
Helena Steinocher ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Human Growth Hormone ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Lipid Membrane ◽  
Human Growth ◽  
Full Length ◽  
Saxs Data ◽  
X Ray ◽  
Human Growth Hormone Receptor

Because of its small size (70 kilodalton) and large content of structural disorder (>50%), the human growth hormone receptor (hGHR) falls between the cracks of conventional high-resolution structural biology methods. Here, we study the structure of the full-length hGHR in nanodiscs with small-angle x-ray scattering (SAXS) as the foundation. We develop an approach that combines SAXS, x-ray diffraction, and NMR spectroscopy data obtained on individual domains and integrate these through molecular dynamics simulations to interpret SAXS data on the full-length hGHR in nanodiscs. The hGHR domains reorient freely, resulting in a broad structural ensemble, emphasizing the need to take an ensemble view on signaling of relevance to disease states. The structure provides the first experimental model of any full-length cytokine receptor in a lipid membrane and exemplifies how integrating experimental data from several techniques computationally may access structures of membrane proteins with long, disordered regions, a widespread phenomenon in biology.

scholarly journals Order and disorder – an integrative structure of the full-length human growth hormone receptor

2020 ◽  
Author(s):  
Noah Kassem ◽  
Raul Araya-Secchi ◽  
Katrine Bugge ◽  
Abigail Barclay ◽  
Helena Steinocher ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Human Growth Hormone ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Lipid Membrane ◽  
Structural Information ◽  
Human Growth ◽  
Full Length ◽  
X Ray ◽  
Human Growth Hormone Receptor

ABSTRACTDespite the many physiological and pathophysiological functions of the human growth hormone receptor (hGHR), a detailed understanding of its modus operandi is hindered by the lack of structural information of the entire receptor at the molecular level. Due to its relatively small size (70 kDa) and large content of structural disorder (>50%), this membrane protein falls between the cracks of conventional high-resolution structural biology methods. Here, we study the structure of the full-length hGHR in nanodiscs with small angle-X-ray scattering (SAXS) as the foundation. We developed an approach in which we combined SAXS, X-ray diffraction and NMR spectroscopy obtained on the individual domains and integrated the data through molecular dynamics simulations to interpret SAXS data on the full-length hGHR in nanodiscs. The structure of the hGHR was determined in its monomeric state and provides the first experimental model of any full-length cytokine receptor in a lipid membrane. Combined, our results highlight that the three domains of the hGHR are free to reorient relative to each other, resulting in a broad structural ensemble. Our work exemplifies how integrating experimental data from several techniques computationally, may enable the characterization of otherwise inaccessible structures of membrane proteins with long disordered regions, a widespread phenomenon in biology. To understand orchestration of cellular signaling by disordered chains, the hGHR is archetypal and its structure emphasizes that we need to take a much broader, ensemble view on signaling.

scholarly journals Crystallization and preliminary X-ray diffraction analysis of the unliganded human growth hormone receptor

2004 ◽  
Vol 60 (12) ◽  
pp. 2380-2382 ◽  
Author(s):  
William J. McKinstry ◽  
Yu Wan ◽  
Julian J. Adams ◽  
Richard J. Brown ◽  
Michael J. Waters ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Diffraction Analysis ◽  
Human Growth Hormone ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Human Growth ◽  
X Ray Diffraction ◽  
X Ray ◽  
Human Growth Hormone Receptor

scholarly journals Mapping of a Cytoplasmic Domain of the Human Growth Hormone Receptor That Regulates Rates of Inactivation of Jak2 and Stat Proteins

1997 ◽  
Vol 272 (17) ◽  
pp. 11128-11132 ◽  
Author(s):  
Rebecca H. Hackett ◽  
Yi-Ding Wang ◽  
Sharon Sweitzer ◽  
Gerald Feldman ◽  
William I. Wood ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Human Growth Hormone ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Human Growth ◽  
Cytoplasmic Domain ◽  
Stat Proteins ◽  
Human Growth Hormone Receptor

Expression of two isoforms of the human growth hormone receptor in normal liver and hepatocarcinoma

1994 ◽  
Vol 103 (1-2) ◽  
pp. 13-20 ◽  
Author(s):  
Nazario Esposito ◽  
Patricia Paterlini ◽  
Paul A. Kelly ◽  
Marie-Catherine Postel-Vinay ◽  
Joelle Finidori
Keyword(s):  
Growth Hormone ◽  
Human Growth Hormone ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Human Growth ◽  
Normal Liver ◽  
Human Growth Hormone Receptor
Sign in / Sign up

Export Citation Format

Share Document