High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor

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

Standard

High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. / Cherezov, Vadim; Rosenbaum, Daniel M; Hanson, Michael A; Rasmussen, Søren Gøgsig Faarup; Thian, Foon Sun; Kobilka, Tong Sun; Choi, Hee-Jung; Kuhn, Peter; Weis, William I; Kobilka, Brian K; Stevens, Raymond C.

In: Science (New York, N.Y.), Vol. 318, No. 5854, 23.11.2007, p. 1258-65.

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

Harvard

Cherezov, V, Rosenbaum, DM, Hanson, MA, Rasmussen, SGF, Thian, FS, Kobilka, TS, Choi, H-J, Kuhn, P, Weis, WI, Kobilka, BK & Stevens, RC 2007, 'High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor', Science (New York, N.Y.), vol. 318, no. 5854, pp. 1258-65. https://doi.org/10.1126/science.1150577

APA

Cherezov, V., Rosenbaum, D. M., Hanson, M. A., Rasmussen, S. G. F., Thian, F. S., Kobilka, T. S., Choi, H-J., Kuhn, P., Weis, W. I., Kobilka, B. K., & Stevens, R. C. (2007). High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science (New York, N.Y.), 318(5854), 1258-65. https://doi.org/10.1126/science.1150577

Vancouver

Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SGF, Thian FS, Kobilka TS et al. High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science (New York, N.Y.). 2007 Nov 23;318(5854):1258-65. https://doi.org/10.1126/science.1150577

Author

Cherezov, Vadim ; Rosenbaum, Daniel M ; Hanson, Michael A ; Rasmussen, Søren Gøgsig Faarup ; Thian, Foon Sun ; Kobilka, Tong Sun ; Choi, Hee-Jung ; Kuhn, Peter ; Weis, William I ; Kobilka, Brian K ; Stevens, Raymond C. / High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. In: Science (New York, N.Y.). 2007 ; Vol. 318, No. 5854. pp. 1258-65.

Bibtex

@article{5a63a168d05d4e2ca3f93b1e47956640,
title = "High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor",
abstract = "Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors constitute the largest family of eukaryotic signal transduction proteins that communicate across the membrane. We report the crystal structure of a human beta2-adrenergic receptor-T4 lysozyme fusion protein bound to the partial inverse agonist carazolol at 2.4 angstrom resolution. The structure provides a high-resolution view of a human G protein-coupled receptor bound to a diffusible ligand. Ligand-binding site accessibility is enabled by the second extracellular loop, which is held out of the binding cavity by a pair of closely spaced disulfide bridges and a short helical segment within the loop. Cholesterol, a necessary component for crystallization, mediates an intriguing parallel association of receptor molecules in the crystal lattice. Although the location of carazolol in the beta2-adrenergic receptor is very similar to that of retinal in rhodopsin, structural differences in the ligand-binding site and other regions highlight the challenges in using rhodopsin as a template model for this large receptor family.",
keywords = "Bacteriophage T4, Binding Sites, Cell Membrane, Cholesterol, Crystallization, Crystallography, X-Ray, Drug Inverse Agonism, Humans, Ligands, Models, Molecular, Muramidase, Propanolamines, Protein Conformation, Protein Folding, Protein Structure, Secondary, Receptors, Adrenergic, beta-2, Recombinant Fusion Proteins, Rhodopsin, Static Electricity",
author = "Vadim Cherezov and Rosenbaum, {Daniel M} and Hanson, {Michael A} and Rasmussen, {S{\o}ren G{\o}gsig Faarup} and Thian, {Foon Sun} and Kobilka, {Tong Sun} and Hee-Jung Choi and Peter Kuhn and Weis, {William I} and Kobilka, {Brian K} and Stevens, {Raymond C}",
year = "2007",
month = nov,
day = "23",
doi = "10.1126/science.1150577",
language = "English",
volume = "318",
pages = "1258--65",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "5854",

}

RIS

TY - JOUR

T1 - High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor

AU - Cherezov, Vadim

AU - Rosenbaum, Daniel M

AU - Hanson, Michael A

AU - Rasmussen, Søren Gøgsig Faarup

AU - Thian, Foon Sun

AU - Kobilka, Tong Sun

AU - Choi, Hee-Jung

AU - Kuhn, Peter

AU - Weis, William I

AU - Kobilka, Brian K

AU - Stevens, Raymond C

PY - 2007/11/23

Y1 - 2007/11/23

N2 - Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors constitute the largest family of eukaryotic signal transduction proteins that communicate across the membrane. We report the crystal structure of a human beta2-adrenergic receptor-T4 lysozyme fusion protein bound to the partial inverse agonist carazolol at 2.4 angstrom resolution. The structure provides a high-resolution view of a human G protein-coupled receptor bound to a diffusible ligand. Ligand-binding site accessibility is enabled by the second extracellular loop, which is held out of the binding cavity by a pair of closely spaced disulfide bridges and a short helical segment within the loop. Cholesterol, a necessary component for crystallization, mediates an intriguing parallel association of receptor molecules in the crystal lattice. Although the location of carazolol in the beta2-adrenergic receptor is very similar to that of retinal in rhodopsin, structural differences in the ligand-binding site and other regions highlight the challenges in using rhodopsin as a template model for this large receptor family.

AB - Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors constitute the largest family of eukaryotic signal transduction proteins that communicate across the membrane. We report the crystal structure of a human beta2-adrenergic receptor-T4 lysozyme fusion protein bound to the partial inverse agonist carazolol at 2.4 angstrom resolution. The structure provides a high-resolution view of a human G protein-coupled receptor bound to a diffusible ligand. Ligand-binding site accessibility is enabled by the second extracellular loop, which is held out of the binding cavity by a pair of closely spaced disulfide bridges and a short helical segment within the loop. Cholesterol, a necessary component for crystallization, mediates an intriguing parallel association of receptor molecules in the crystal lattice. Although the location of carazolol in the beta2-adrenergic receptor is very similar to that of retinal in rhodopsin, structural differences in the ligand-binding site and other regions highlight the challenges in using rhodopsin as a template model for this large receptor family.

KW - Bacteriophage T4

KW - Binding Sites

KW - Cell Membrane

KW - Cholesterol

KW - Crystallization

KW - Crystallography, X-Ray

KW - Drug Inverse Agonism

KW - Humans

KW - Ligands

KW - Models, Molecular

KW - Muramidase

KW - Propanolamines

KW - Protein Conformation

KW - Protein Folding

KW - Protein Structure, Secondary

KW - Receptors, Adrenergic, beta-2

KW - Recombinant Fusion Proteins

KW - Rhodopsin

KW - Static Electricity

U2 - 10.1126/science.1150577

DO - 10.1126/science.1150577

M3 - Journal article

C2 - 17962520

VL - 318

SP - 1258

EP - 1265

JO - Science

JF - Science

SN - 0036-8075

IS - 5854

ER -

ID: 120588695