We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Structure of a nanobody-stabilized active state of the β<sub>2</sub> adrenoceptor.
- Authors
Rasmussen, Søren G. F.; Hee-Jung Choi; Juan Jose Fung; Pardon, Els; Casarosa, Paola; Chae, Pil Seok; DeVree, Brian T.; Rosenbaum, Daniel M.; Foon Sun Thian; Kobilka, Tong Sun; Schnapp, Andreas; Konetzki, Ingo; Sunahara, Roger K.; Gellman, Samuel H.; Pautsch, Alexander; Steyaert, Jan; Weis, William I.; Kobilka, Brian K.
- 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.
- Publication
Nature, 2011, Vol 469, Issue 7329, p175
- ISSN
0028-0836
- Publication type
Academic Journal
- DOI
10.1038/nature09648