First structure of a complex between a G protein coupled receptor (GPCR) and its G protein revealed
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Figure: The β2
adrenergic receptor is shown in blue, the agonist is shown as green spheres,
Gαs is shown in orange, Gβ is shown in yellow, and Gγ is
shown in green. |
Brian Kobilka group (Stanford University) and collaborators
Recently, a collaborative research group headed by Brian
Kobilka succeeded in obtaining the first high resolution structure of a
GPCR-G protein complex: the β2 adrenergic receptor-Gs protein
complex. GPCRs constitute a family of over 800 proteins with common
structural and functional properties. GCPRs have seven transmembrane segments
that transmit signals from an extracellular hormone or neurotransmitter
agonist across the cell membrane to an intracellular signaling protein, a
heterotrimeric guanine nucleotide binding protein (G protein). The
agonist-GPCR-G protein complex is responsible for a majority of cellular
responses to hormones and neurotransmitters. Consequently, GPCRs are one of
the largest groups of targets for drug discovery. The β2
adrenergic receptor (β2AR) is a GPCR that responds to
adrenaline and noradrenaline and activates Gs, the stimulatory G protein for
adenylyl cyclase. The structure of the β2AR-Gs complex was
solved with the help of the high-intensity mini-beam and rastering capabilities
at the GM/CA beamlines. This structure provides the first high-resolution
picture of transmembrane signaling by a GPCR.
Citation: Rasmussen SG, DeVree BT, Zou Y, Kruse AC, Chung
KY, Kobilka TS, Thian FS, Chae PS, Pardon E, Calinski D, Mathiesen JM, Shah
ST, Lyons JA, Caffrey M, Gellman SH, Steyaert J, Skiniotis G, Weis WI,
Sunahara RK, Kobilka BK. Crystal structure of the
β2 adrenergic receptor-Gs protein complex. Nature. 2011 Jul
19;477(7366):549-55. doi: 10.1038/nature10361.
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