Structure of a nanobody-stabilized active state of the β2 adrenoceptor

Søren G. F. Rasmussen, Hee-Jung Choi, Juan Jose Fung, Els Pardon, Paola Casarosa, Pil Seok Chae, Brian T. DeVree, Daniel M. Rosenbaum, Foon Sun Thian, Tong Sun Kobilka, Andreas Schnapp, Ingo Konetzki, Roger K. Sunahara, Samuel H. Gellman, Alexander Pautsch, Jan Steyaert, William I. Weis () and Brian K. Kobilka ()
Additional contact information
Søren G. F. Rasmussen: Stanford University School of Medicine, 279 Campus Drive
Hee-Jung Choi: Stanford University School of Medicine, 279 Campus Drive
Juan Jose Fung: Stanford University School of Medicine, 279 Campus Drive
Els Pardon: Vlaams Instituut voor Biotechnologie (VIB), Vrije Universiteit Brussel, B-1050 Brussels, Belgium
Paola Casarosa: Boehringer Ingelheim Pharma GmbH & Co. KG
Pil Seok Chae: University of Wisconsin
Brian T. DeVree: University of Michigan Medical School
Daniel M. Rosenbaum: Stanford University School of Medicine, 279 Campus Drive
Foon Sun Thian: Stanford University School of Medicine, 279 Campus Drive
Tong Sun Kobilka: Stanford University School of Medicine, 279 Campus Drive
Andreas Schnapp: Boehringer Ingelheim Pharma GmbH & Co. KG
Ingo Konetzki: Boehringer Ingelheim Pharma GmbH & Co. KG
Roger K. Sunahara: University of Michigan Medical School
Samuel H. Gellman: University of Wisconsin
Alexander Pautsch: Boehringer Ingelheim Pharma GmbH & Co. KG
Jan Steyaert: Vlaams Instituut voor Biotechnologie (VIB), Vrije Universiteit Brussel, B-1050 Brussels, Belgium
William I. Weis: Stanford University School of Medicine, 279 Campus Drive
Brian K. Kobilka: Stanford University School of Medicine, 279 Campus Drive

Nature, 2011, vol. 469, issue 7329, 175-180

Abstract: Abstract G protein coupled receptors (GPCRs) exhibit a spectrum of functional behaviours in response to natural and synthetic ligands. Recent crystal structures provide insights into inactive states of several GPCRs. Efforts to obtain an agonist-bound active-state GPCR structure have proven difficult due to the inherent instability of this state in the absence of a G protein. We generated a camelid antibody fragment (nanobody) to the human β2 adrenergic receptor (β2AR) that exhibits G protein-like behaviour, and obtained an agonist-bound, active-state crystal structure of the receptor-nanobody complex. Comparison with the inactive β2AR structure reveals subtle changes in the binding pocket; however, these small changes are associated with an 11 Å outward movement of the cytoplasmic end of transmembrane segment 6, and rearrangements of transmembrane segments 5 and 7 that are remarkably similar to those observed in opsin, an active form of rhodopsin. This structure provides insights into the process of agonist binding and activation.

Date: 2011
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/nature09648 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:469:y:2011:i:7329:d:10.1038_nature09648

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature09648

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().