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

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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.

I: Science Advances, Bind 7, Nr. 27, eabh3805, 2021.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

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 2021, 'Order and disorder - An integrative structure of the full-length human growth hormone receptor', Science Advances, bind 7, nr. 27, eabh3805. https://doi.org/10.1126/sciadv.abh3805

APA

Kassem, N., Araya-Secchi, R., Bugge, K., Barclay, A., Steinocher, H., Khondker, A., Wang, Y., Lenard, A. J., Bürck, J., Sahin, C., Ulrich, A. S., Landreh, M., Pedersen, M. C., Rheinstädter, M. C., Pedersen, P. A., Lindorff-Larsen, K., Arleth, L., & Kragelund, B. B. (2021). Order and disorder - An integrative structure of the full-length human growth hormone receptor. Science Advances, 7(27), [eabh3805]. https://doi.org/10.1126/sciadv.abh3805

Vancouver

Kassem N, Araya-Secchi R, Bugge K, Barclay A, Steinocher H, Khondker A o.a. Order and disorder - An integrative structure of the full-length human growth hormone receptor. Science Advances. 2021;7(27). eabh3805. https://doi.org/10.1126/sciadv.abh3805

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. / Order and disorder - An integrative structure of the full-length human growth hormone receptor. I: Science Advances. 2021 ; Bind 7, Nr. 27.

Bibtex

@article{92dc7b4347414337bc97cd6d72ffa848,

title = "Order and disorder - An integrative structure of the full-length human growth hormone receptor",

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.",

author = "Noah Kassem and Raul Araya-Secchi and Katrine Bugge and Abigail Barclay and Helena Steinocher and Adree Khondker and Yong Wang and Lenard, {Aneta J.} and Jochen B{\"u}rck and Cagla Sahin and Ulrich, {Anne S.} and Michael Landreh and Pedersen, {Martin Cramer} and Rheinst{\"a}dter, {Maikel C.} and Pedersen, {Per Amstrup} and Kresten Lindorff-Larsen and Lise Arleth and Kragelund, {Birthe B.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2021 The Authors, some rights reserved.",

year = "2021",

doi = "10.1126/sciadv.abh3805",

language = "English",

volume = "7",

journal = "Science advances",

issn = "2375-2548",

publisher = "American Association for the Advancement of Science",

number = "27",

}

RIS

TY - JOUR

T1 - Order and disorder - An integrative structure of the full-length human growth hormone receptor

AU - Kassem, Noah

AU - Araya-Secchi, Raul

AU - Bugge, Katrine

AU - Barclay, Abigail

AU - Steinocher, Helena

AU - Khondker, Adree

AU - Wang, Yong

AU - Lenard, Aneta J.

AU - Bürck, Jochen

AU - Sahin, Cagla

AU - Ulrich, Anne S.

AU - Landreh, Michael

AU - Pedersen, Martin Cramer

AU - Rheinstädter, Maikel C.

AU - Pedersen, Per Amstrup

AU - Lindorff-Larsen, Kresten

AU - Arleth, Lise

AU - Kragelund, Birthe B.

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1126/sciadv.abh3805

DO - 10.1126/sciadv.abh3805

M3 - Journal article

C2 - 34193419

AN - SCOPUS:85109019350

VL - 7

JO - Science advances

JF - Science advances

SN - 2375-2548

IS - 27

M1 - eabh3805

ER -

ID: 275991610

Niels Bohr Institutet