The role of protein “Stability patches” in molecular recognition: A case study of the human growth hormone-receptor complex

2015 ◽  
Vol 37 (10) ◽  
pp. 913-919 ◽  
Author(s):  
Roman Osman ◽  
Mihaly Mezei ◽  
Stanislav Engel
2021 ◽  
Vol 7 (27) ◽  
pp. eabh3805
Author(s):  
Noah Kassem ◽  
Raul Araya-Secchi ◽  
Katrine Bugge ◽  
Abigail Barclay ◽  
Helena Steinocher ◽  
...  

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.


1997 ◽  
Vol 272 (17) ◽  
pp. 11128-11132 ◽  
Author(s):  
Rebecca H. Hackett ◽  
Yi-Ding Wang ◽  
Sharon Sweitzer ◽  
Gerald Feldman ◽  
William I. Wood ◽  
...  

1994 ◽  
Vol 103 (1-2) ◽  
pp. 13-20 ◽  
Author(s):  
Nazario Esposito ◽  
Patricia Paterlini ◽  
Paul A. Kelly ◽  
Marie-Catherine Postel-Vinay ◽  
Joelle Finidori

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