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Order and disorder—An integrative structure of the full-length 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-ang...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245047/ https://www.ncbi.nlm.nih.gov/pubmed/34193419 http://dx.doi.org/10.1126/sciadv.abh3805 |
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author | Kassem, Noah Araya-Secchi, Raul Bugge, Katrine Barclay, Abigail Steinocher, Helena Khondker, Adree Wang, Yong Lenard, Aneta J. Bürck, Jochen Sahin, Cagla Ulrich, Anne S. Landreh, Michael Pedersen, Martin Cramer Rheinstädter, Maikel C. Pedersen, Per Amstrup Lindorff-Larsen, Kresten Arleth, Lise Kragelund, Birthe B. |
author_facet | Kassem, Noah Araya-Secchi, Raul Bugge, Katrine Barclay, Abigail Steinocher, Helena Khondker, Adree Wang, Yong Lenard, Aneta J. Bürck, Jochen Sahin, Cagla Ulrich, Anne S. Landreh, Michael Pedersen, Martin Cramer Rheinstädter, Maikel C. Pedersen, Per Amstrup Lindorff-Larsen, Kresten Arleth, Lise Kragelund, Birthe B. |
author_sort | Kassem, Noah |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8245047 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-82450472021-07-13 Order and disorder—An integrative structure of the full-length human growth hormone receptor Kassem, Noah Araya-Secchi, Raul Bugge, Katrine Barclay, Abigail Steinocher, Helena Khondker, Adree Wang, Yong Lenard, Aneta J. Bürck, Jochen Sahin, Cagla Ulrich, Anne S. Landreh, Michael Pedersen, Martin Cramer Rheinstädter, Maikel C. Pedersen, Per Amstrup Lindorff-Larsen, Kresten Arleth, Lise Kragelund, Birthe B. Sci Adv Research Articles 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. American Association for the Advancement of Science 2021-06-30 /pmc/articles/PMC8245047/ /pubmed/34193419 http://dx.doi.org/10.1126/sciadv.abh3805 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Kassem, Noah Araya-Secchi, Raul Bugge, Katrine Barclay, Abigail Steinocher, Helena Khondker, Adree Wang, Yong Lenard, Aneta J. Bürck, Jochen Sahin, Cagla Ulrich, Anne S. Landreh, Michael Pedersen, Martin Cramer Rheinstädter, Maikel C. Pedersen, Per Amstrup Lindorff-Larsen, Kresten Arleth, Lise Kragelund, Birthe B. Order and disorder—An integrative structure of the full-length human growth hormone receptor |
title | Order and disorder—An integrative structure of the full-length human growth hormone receptor |
title_full | Order and disorder—An integrative structure of the full-length human growth hormone receptor |
title_fullStr | Order and disorder—An integrative structure of the full-length human growth hormone receptor |
title_full_unstemmed | Order and disorder—An integrative structure of the full-length human growth hormone receptor |
title_short | Order and disorder—An integrative structure of the full-length human growth hormone receptor |
title_sort | order and disorder—an integrative structure of the full-length human growth hormone receptor |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245047/ https://www.ncbi.nlm.nih.gov/pubmed/34193419 http://dx.doi.org/10.1126/sciadv.abh3805 |
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