Crystal structure of the β2 adrenergic receptor-Gs protein complex
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Crystal structure of the β2 adrenergic receptor-Gs protein complex. / Rasmussen, Søren Gøgsig Faarup; DeVree, Brian T; Zou, Yaozhong; Kruse, Andrew C; Chung, Ka Young; Kobilka, Tong Sun; Thian, Foon Sun; Chae, Pil Seok; Pardon, Els; Calinski, Diane; Mathiesen, Jesper M; Shah, Syed T A; Lyons, Joseph A; Caffrey, Martin; Gellman, Samuel H; Steyaert, Jan; Skiniotis, Georgios; Weis, William I; Sunahara, Roger K; Kobilka, Brian K.
In: Nature, Vol. 477, No. 7366, 29.09.2011, p. 549-55.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Crystal structure of the β2 adrenergic receptor-Gs protein complex
AU - Rasmussen, Søren Gøgsig Faarup
AU - DeVree, Brian T
AU - Zou, Yaozhong
AU - Kruse, Andrew C
AU - Chung, Ka Young
AU - Kobilka, Tong Sun
AU - Thian, Foon Sun
AU - Chae, Pil Seok
AU - Pardon, Els
AU - Calinski, Diane
AU - Mathiesen, Jesper M
AU - Shah, Syed T A
AU - Lyons, Joseph A
AU - Caffrey, Martin
AU - Gellman, Samuel H
AU - Steyaert, Jan
AU - Skiniotis, Georgios
AU - Weis, William I
AU - Sunahara, Roger K
AU - Kobilka, Brian K
N1 - © 2011 Macmillan Publishers Limited. All rights reserved
PY - 2011/9/29
Y1 - 2011/9/29
N2 - G protein-coupled receptors (GPCRs) are responsible for the majority of cellular responses to hormones and neurotransmitters as well as the senses of sight, olfaction and taste. The paradigm of GPCR signalling is the activation of a heterotrimeric GTP binding protein (G protein) by an agonist-occupied receptor. The β(2) adrenergic receptor (β(2)AR) activation of Gs, the stimulatory G protein for adenylyl cyclase, has long been a model system for GPCR signalling. Here we present the crystal structure of the active state ternary complex composed of agonist-occupied monomeric β(2)AR and nucleotide-free Gs heterotrimer. The principal interactions between the β(2)AR and Gs involve the amino- and carboxy-terminal α-helices of Gs, with conformational changes propagating to the nucleotide-binding pocket. The largest conformational changes in the β(2)AR include a 14 Å outward movement at the cytoplasmic end of transmembrane segment 6 (TM6) and an α-helical extension of the cytoplasmic end of TM5. The most surprising observation is a major displacement of the α-helical domain of Gαs relative to the Ras-like GTPase domain. This crystal structure represents the first high-resolution view of transmembrane signalling by a GPCR.
AB - G protein-coupled receptors (GPCRs) are responsible for the majority of cellular responses to hormones and neurotransmitters as well as the senses of sight, olfaction and taste. The paradigm of GPCR signalling is the activation of a heterotrimeric GTP binding protein (G protein) by an agonist-occupied receptor. The β(2) adrenergic receptor (β(2)AR) activation of Gs, the stimulatory G protein for adenylyl cyclase, has long been a model system for GPCR signalling. Here we present the crystal structure of the active state ternary complex composed of agonist-occupied monomeric β(2)AR and nucleotide-free Gs heterotrimer. The principal interactions between the β(2)AR and Gs involve the amino- and carboxy-terminal α-helices of Gs, with conformational changes propagating to the nucleotide-binding pocket. The largest conformational changes in the β(2)AR include a 14 Å outward movement at the cytoplasmic end of transmembrane segment 6 (TM6) and an α-helical extension of the cytoplasmic end of TM5. The most surprising observation is a major displacement of the α-helical domain of Gαs relative to the Ras-like GTPase domain. This crystal structure represents the first high-resolution view of transmembrane signalling by a GPCR.
KW - Adrenergic beta-2 Receptor Agonists
KW - Animals
KW - Catalytic Domain
KW - Cattle
KW - Crystallization
KW - Crystallography, X-Ray
KW - Enzyme Activation
KW - GTP-Binding Protein alpha Subunits, Gs
KW - Models, Molecular
KW - Multiprotein Complexes
KW - Protein Binding
KW - Rats
KW - Receptors, Adrenergic, beta-2
U2 - 10.1038/nature10361
DO - 10.1038/nature10361
M3 - Journal article
C2 - 21772288
VL - 477
SP - 549
EP - 555
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7366
ER -
ID: 120588243