3SN6

Crystal structure of the beta2 adrenergic receptor-Gs protein complex

Summary for 3SN6

• Entry DOI: 10.2210/pdb3sn6/pdb
• Descriptor: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (6 entities in total)
• Functional Keywords: seven transmembrane receptor, nanobody, g protein-coupled receptor, gpcr, signal transduction, g protein signaling, signaling protein-hydrolase complex, signaling protein/hydrolase
• Biological source: Bos taurus (Bovine); More
• Total number of polymer chains: 5
• Total formula weight: 164492.58

Authors

Rasmussen, S.G.F.,DeVree, B.T.,Zou, Y.,Kruse, A.C.,Chung, K.Y.,Kobilka, T.S.,Thian, F.S.,Chae, P.S.,Pardon, E.,Calinski, D.,Mathiesen, J.M.,Shah, S.T.A.,Lyons, J.A.,Caffrey, M.,Gellman, S.H.,Steyaert, J.,Skiniotis, G.,Weis, W.I.,Sunahara, R.K.,Kobilka, B.K. (deposition date: 2011-06-28, release date: 2011-07-20, Last modification date: 2024-11-20)

Primary citation

Rasmussen, S.G.,DeVree, B.T.,Zou, Y.,Kruse, A.C.,Chung, K.Y.,Kobilka, T.S.,Thian, F.S.,Chae, P.S.,Pardon, E.,Calinski, D.,Mathiesen, J.M.,Shah, S.T.,Lyons, J.A.,Caffrey, M.,Gellman, S.H.,Steyaert, J.,Skiniotis, G.,Weis, W.I.,Sunahara, R.K.,Kobilka, B.K.
Crystal structure of the beta2 adrenergic receptor-Gs protein complex
Nature, 477:549-555, 2011

PubMed Abstract: 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.

PubMed: 21772288
DOI: 10.1038/nature10361

Experimental method

X-RAY DIFFRACTION (3.2 Å)