Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kassem, N; Araya-Secchi, R; Bugge, K; Barclay, A; Steinocher, H; Khondker, A; Wang, Y; Lenard, AJ; Bürck, J; Sahin, C; Ulrich, AS; Landreh, M; Pedersen, MC; Rheinstädter, MC; Pedersen, PA; Lindorff-Larsen, K; Arleth, L; Kragelund, BB.
Order and disorder-An integrative structure of the full-length human growth hormone receptor.
Sci Adv. 2021; 7(27):
Doi: 10.1126/sciadv.abh3805
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- Co-Autor*innen der Med Uni Graz
- Lenard Aneta
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- 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.