Crystal structure of the human beta2 adrenergic G-protein-coupled receptor

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

Standard

Crystal structure of the human beta2 adrenergic G-protein-coupled receptor. / Rasmussen, Søren Gøgsig Faarup; Choi, Hee-Jung; Rosenbaum, Daniel M; Kobilka, Tong Sun; Thian, Foon Sun; Edwards, Patricia C; Burghammer, Manfred; Ratnala, Venkata R P; Sanishvili, Ruslan; Fischetti, Robert F; Schertler, Gebhard F X; Weis, William I; Kobilka, Brian K.

In: Nature, Vol. 450, No. 7168, 15.11.2007, p. 383-7.

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

Harvard

Rasmussen, SGF, Choi, H-J, Rosenbaum, DM, Kobilka, TS, Thian, FS, Edwards, PC, Burghammer, M, Ratnala, VRP, Sanishvili, R, Fischetti, RF, Schertler, GFX, Weis, WI & Kobilka, BK 2007, 'Crystal structure of the human beta2 adrenergic G-protein-coupled receptor', Nature, vol. 450, no. 7168, pp. 383-7. https://doi.org/10.1038/nature06325

APA

Rasmussen, S. G. F., Choi, H-J., Rosenbaum, D. M., Kobilka, T. S., Thian, F. S., Edwards, P. C., Burghammer, M., Ratnala, V. R. P., Sanishvili, R., Fischetti, R. F., Schertler, G. F. X., Weis, W. I., & Kobilka, B. K. (2007). Crystal structure of the human beta2 adrenergic G-protein-coupled receptor. Nature, 450(7168), 383-7. https://doi.org/10.1038/nature06325

Vancouver

Rasmussen SGF, Choi H-J, Rosenbaum DM, Kobilka TS, Thian FS, Edwards PC et al. Crystal structure of the human beta2 adrenergic G-protein-coupled receptor. Nature. 2007 Nov 15;450(7168):383-7. https://doi.org/10.1038/nature06325

Author

Rasmussen, Søren Gøgsig Faarup ; Choi, Hee-Jung ; Rosenbaum, Daniel M ; Kobilka, Tong Sun ; Thian, Foon Sun ; Edwards, Patricia C ; Burghammer, Manfred ; Ratnala, Venkata R P ; Sanishvili, Ruslan ; Fischetti, Robert F ; Schertler, Gebhard F X ; Weis, William I ; Kobilka, Brian K. / Crystal structure of the human beta2 adrenergic G-protein-coupled receptor. In: Nature. 2007 ; Vol. 450, No. 7168. pp. 383-7.

Bibtex

@article{0c64e5b736d345058f3ffcf4551656fd,
title = "Crystal structure of the human beta2 adrenergic G-protein-coupled receptor",
abstract = "Structural analysis of G-protein-coupled receptors (GPCRs) for hormones and neurotransmitters has been hindered by their low natural abundance, inherent structural flexibility, and instability in detergent solutions. Here we report a structure of the human beta2 adrenoceptor (beta2AR), which was crystallized in a lipid environment when bound to an inverse agonist and in complex with a Fab that binds to the third intracellular loop. Diffraction data were obtained by high-brilliance microcrystallography and the structure determined at 3.4 A/3.7 A resolution. The cytoplasmic ends of the beta2AR transmembrane segments and the connecting loops are well resolved, whereas the extracellular regions of the beta2AR are not seen. The beta2AR structure differs from rhodopsin in having weaker interactions between the cytoplasmic ends of transmembrane (TM)3 and TM6, involving the conserved E/DRY sequences. These differences may be responsible for the relatively high basal activity and structural instability of the beta2AR, and contribute to the challenges in obtaining diffraction-quality crystals of non-rhodopsin GPCRs.",
keywords = "Adrenergic beta-2 Receptor Antagonists, Animals, Cell Line, Crystallization, Crystallography, X-Ray, Drug Inverse Agonism, Humans, Immunoglobulin Fab Fragments, Leucine, Lipids, Models, Molecular, Protein Conformation, Receptors, Adrenergic, beta-2, Rhodopsin, Spodoptera",
author = "Rasmussen, {S{\o}ren G{\o}gsig Faarup} and Hee-Jung Choi and Rosenbaum, {Daniel M} and Kobilka, {Tong Sun} and Thian, {Foon Sun} and Edwards, {Patricia C} and Manfred Burghammer and Ratnala, {Venkata R P} and Ruslan Sanishvili and Fischetti, {Robert F} and Schertler, {Gebhard F X} and Weis, {William I} and Kobilka, {Brian K}",
year = "2007",
month = nov,
day = "15",
doi = "10.1038/nature06325",
language = "English",
volume = "450",
pages = "383--7",
journal = "Nature",
issn = "0028-0836",
publisher = "nature publishing group",
number = "7168",

}

RIS

TY - JOUR

T1 - Crystal structure of the human beta2 adrenergic G-protein-coupled receptor

AU - Rasmussen, Søren Gøgsig Faarup

AU - Choi, Hee-Jung

AU - Rosenbaum, Daniel M

AU - Kobilka, Tong Sun

AU - Thian, Foon Sun

AU - Edwards, Patricia C

AU - Burghammer, Manfred

AU - Ratnala, Venkata R P

AU - Sanishvili, Ruslan

AU - Fischetti, Robert F

AU - Schertler, Gebhard F X

AU - Weis, William I

AU - Kobilka, Brian K

PY - 2007/11/15

Y1 - 2007/11/15

N2 - Structural analysis of G-protein-coupled receptors (GPCRs) for hormones and neurotransmitters has been hindered by their low natural abundance, inherent structural flexibility, and instability in detergent solutions. Here we report a structure of the human beta2 adrenoceptor (beta2AR), which was crystallized in a lipid environment when bound to an inverse agonist and in complex with a Fab that binds to the third intracellular loop. Diffraction data were obtained by high-brilliance microcrystallography and the structure determined at 3.4 A/3.7 A resolution. The cytoplasmic ends of the beta2AR transmembrane segments and the connecting loops are well resolved, whereas the extracellular regions of the beta2AR are not seen. The beta2AR structure differs from rhodopsin in having weaker interactions between the cytoplasmic ends of transmembrane (TM)3 and TM6, involving the conserved E/DRY sequences. These differences may be responsible for the relatively high basal activity and structural instability of the beta2AR, and contribute to the challenges in obtaining diffraction-quality crystals of non-rhodopsin GPCRs.

AB - Structural analysis of G-protein-coupled receptors (GPCRs) for hormones and neurotransmitters has been hindered by their low natural abundance, inherent structural flexibility, and instability in detergent solutions. Here we report a structure of the human beta2 adrenoceptor (beta2AR), which was crystallized in a lipid environment when bound to an inverse agonist and in complex with a Fab that binds to the third intracellular loop. Diffraction data were obtained by high-brilliance microcrystallography and the structure determined at 3.4 A/3.7 A resolution. The cytoplasmic ends of the beta2AR transmembrane segments and the connecting loops are well resolved, whereas the extracellular regions of the beta2AR are not seen. The beta2AR structure differs from rhodopsin in having weaker interactions between the cytoplasmic ends of transmembrane (TM)3 and TM6, involving the conserved E/DRY sequences. These differences may be responsible for the relatively high basal activity and structural instability of the beta2AR, and contribute to the challenges in obtaining diffraction-quality crystals of non-rhodopsin GPCRs.

KW - Adrenergic beta-2 Receptor Antagonists

KW - Animals

KW - Cell Line

KW - Crystallization

KW - Crystallography, X-Ray

KW - Drug Inverse Agonism

KW - Humans

KW - Immunoglobulin Fab Fragments

KW - Leucine

KW - Lipids

KW - Models, Molecular

KW - Protein Conformation

KW - Receptors, Adrenergic, beta-2

KW - Rhodopsin

KW - Spodoptera

U2 - 10.1038/nature06325

DO - 10.1038/nature06325

M3 - Journal article

C2 - 17952055

VL - 450

SP - 383

EP - 387

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7168

ER -

ID: 120588937