Structure of a nanobody-stabilized active state of the β(2) adrenoceptor

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Structure of a nanobody-stabilized active state of the β(2) adrenoceptor. / Rasmussen, Søren Gøgsig Faarup; Choi, Hee-Jung; Fung, Juan Jose; Pardon, Els; Casarosa, Paola; Chae, Pil Seok; Devree, Brian T; Rosenbaum, Daniel M; Thian, Foon Sun; Kobilka, Tong Sun; Schnapp, Andreas; Konetzki, Ingo; Sunahara, Roger K; Gellman, Samuel H; Pautsch, Alexander; Steyaert, Jan; Weis, William I; Kobilka, Brian K.

In: Nature, Vol. 469, No. 7329, 13.01.2011, p. 175-80.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Rasmussen, SGF, Choi, H-J, Fung, JJ, Pardon, E, Casarosa, P, Chae, PS, Devree, BT, Rosenbaum, DM, Thian, FS, Kobilka, TS, Schnapp, A, Konetzki, I, Sunahara, RK, Gellman, SH, Pautsch, A, Steyaert, J, Weis, WI & Kobilka, BK 2011, 'Structure of a nanobody-stabilized active state of the β(2) adrenoceptor', Nature, vol. 469, no. 7329, pp. 175-80. https://doi.org/10.1038/nature09648

APA

Rasmussen, S. G. F., Choi, H-J., Fung, J. J., Pardon, E., Casarosa, P., Chae, P. S., Devree, B. T., Rosenbaum, D. M., Thian, F. S., Kobilka, T. S., Schnapp, A., Konetzki, I., Sunahara, R. K., Gellman, S. H., Pautsch, A., Steyaert, J., Weis, W. I., & Kobilka, B. K. (2011). Structure of a nanobody-stabilized active state of the β(2) adrenoceptor. Nature, 469(7329), 175-80. https://doi.org/10.1038/nature09648

Vancouver

Rasmussen SGF, Choi H-J, Fung JJ, Pardon E, Casarosa P, Chae PS et al. Structure of a nanobody-stabilized active state of the β(2) adrenoceptor. Nature. 2011 Jan 13;469(7329):175-80. https://doi.org/10.1038/nature09648

Author

Rasmussen, Søren Gøgsig Faarup ; Choi, Hee-Jung ; Fung, Juan Jose ; Pardon, Els ; Casarosa, Paola ; Chae, Pil Seok ; Devree, Brian T ; Rosenbaum, Daniel M ; Thian, Foon Sun ; Kobilka, Tong Sun ; Schnapp, Andreas ; Konetzki, Ingo ; Sunahara, Roger K ; Gellman, Samuel H ; Pautsch, Alexander ; Steyaert, Jan ; Weis, William I ; Kobilka, Brian K. / Structure of a nanobody-stabilized active state of the β(2) adrenoceptor. In: Nature. 2011 ; Vol. 469, No. 7329. pp. 175-80.

Bibtex

@article{19f666fd86b44b2da53a957e2f136c5e,
title = "Structure of a nanobody-stabilized active state of the β(2) adrenoceptor",
abstract = "G protein coupled receptors (GPCRs) exhibit a spectrum of functional behaviours in response to natural and synthetic ligands. Recent crystal structures provide insights into inactive states of several GPCRs. Efforts to obtain an agonist-bound active-state GPCR structure have proven difficult due to the inherent instability of this state in the absence of a G protein. We generated a camelid antibody fragment (nanobody) to the human β(2) adrenergic receptor (β(2)AR) that exhibits G protein-like behaviour, and obtained an agonist-bound, active-state crystal structure of the receptor-nanobody complex. Comparison with the inactive β(2)AR structure reveals subtle changes in the binding pocket; however, these small changes are associated with an 11 {\AA} outward movement of the cytoplasmic end of transmembrane segment 6, and rearrangements of transmembrane segments 5 and 7 that are remarkably similar to those observed in opsin, an active form of rhodopsin. This structure provides insights into the process of agonist binding and activation.",
keywords = "Adrenergic beta-2 Receptor Agonists, Animals, Binding Sites, Camelids, New World, Crystallography, X-Ray, Drug Inverse Agonism, Humans, Immunoglobulin Fragments, Ligands, Models, Molecular, Movement, Nanostructures, Opsins, Propanolamines, Protein Conformation, Protein Stability, Receptors, Adrenergic, beta-2, Viral Proteins",
author = "Rasmussen, {S{\o}ren G{\o}gsig Faarup} and Hee-Jung Choi and Fung, {Juan Jose} and Els Pardon and Paola Casarosa and Chae, {Pil Seok} and Devree, {Brian T} and Rosenbaum, {Daniel M} and Thian, {Foon Sun} and Kobilka, {Tong Sun} and Andreas Schnapp and Ingo Konetzki and Sunahara, {Roger K} and Gellman, {Samuel H} and Alexander Pautsch and Jan Steyaert and Weis, {William I} and Kobilka, {Brian K}",
year = "2011",
month = jan,
day = "13",
doi = "10.1038/nature09648",
language = "English",
volume = "469",
pages = "175--80",
journal = "Nature",
issn = "0028-0836",
publisher = "nature publishing group",
number = "7329",

}

RIS

TY - JOUR

T1 - Structure of a nanobody-stabilized active state of the β(2) adrenoceptor

AU - Rasmussen, Søren Gøgsig Faarup

AU - Choi, Hee-Jung

AU - Fung, Juan Jose

AU - Pardon, Els

AU - Casarosa, Paola

AU - Chae, Pil Seok

AU - Devree, Brian T

AU - Rosenbaum, Daniel M

AU - Thian, Foon Sun

AU - Kobilka, Tong Sun

AU - Schnapp, Andreas

AU - Konetzki, Ingo

AU - Sunahara, Roger K

AU - Gellman, Samuel H

AU - Pautsch, Alexander

AU - Steyaert, Jan

AU - Weis, William I

AU - Kobilka, Brian K

PY - 2011/1/13

Y1 - 2011/1/13

N2 - G protein coupled receptors (GPCRs) exhibit a spectrum of functional behaviours in response to natural and synthetic ligands. Recent crystal structures provide insights into inactive states of several GPCRs. Efforts to obtain an agonist-bound active-state GPCR structure have proven difficult due to the inherent instability of this state in the absence of a G protein. We generated a camelid antibody fragment (nanobody) to the human β(2) adrenergic receptor (β(2)AR) that exhibits G protein-like behaviour, and obtained an agonist-bound, active-state crystal structure of the receptor-nanobody complex. Comparison with the inactive β(2)AR structure reveals subtle changes in the binding pocket; however, these small changes are associated with an 11 Å outward movement of the cytoplasmic end of transmembrane segment 6, and rearrangements of transmembrane segments 5 and 7 that are remarkably similar to those observed in opsin, an active form of rhodopsin. This structure provides insights into the process of agonist binding and activation.

AB - G protein coupled receptors (GPCRs) exhibit a spectrum of functional behaviours in response to natural and synthetic ligands. Recent crystal structures provide insights into inactive states of several GPCRs. Efforts to obtain an agonist-bound active-state GPCR structure have proven difficult due to the inherent instability of this state in the absence of a G protein. We generated a camelid antibody fragment (nanobody) to the human β(2) adrenergic receptor (β(2)AR) that exhibits G protein-like behaviour, and obtained an agonist-bound, active-state crystal structure of the receptor-nanobody complex. Comparison with the inactive β(2)AR structure reveals subtle changes in the binding pocket; however, these small changes are associated with an 11 Å outward movement of the cytoplasmic end of transmembrane segment 6, and rearrangements of transmembrane segments 5 and 7 that are remarkably similar to those observed in opsin, an active form of rhodopsin. This structure provides insights into the process of agonist binding and activation.

KW - Adrenergic beta-2 Receptor Agonists

KW - Animals

KW - Binding Sites

KW - Camelids, New World

KW - Crystallography, X-Ray

KW - Drug Inverse Agonism

KW - Humans

KW - Immunoglobulin Fragments

KW - Ligands

KW - Models, Molecular

KW - Movement

KW - Nanostructures

KW - Opsins

KW - Propanolamines

KW - Protein Conformation

KW - Protein Stability

KW - Receptors, Adrenergic, beta-2

KW - Viral Proteins

U2 - 10.1038/nature09648

DO - 10.1038/nature09648

M3 - Journal article

C2 - 21228869

VL - 469

SP - 175

EP - 180

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7329

ER -

ID: 120588433