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Order and disorder--An integrative structure of the full-length human growth hormone receptor.
- Source :
-
Science Advances . 6/30/2021, Vol. 7 Issue 27, p1-19. 19p. - Publication Year :
- 2021
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 23752548
- Volume :
- 7
- Issue :
- 27
- Database :
- Academic Search Index
- Journal :
- Science Advances
- Publication Type :
- Academic Journal
- Accession number :
- 173134953
- Full Text :
- https://doi.org/10.1126/sciadv.abh3805