Structure of a nanobody-stabilized active state of the beta(2) adrenoceptor
- Authors
- Rasmussen, Soren G. F.; Choi, Hee-Jung; Fung, Juan Jose; Pardon, Els; Casarosa, Paola; Chae, Pil Seok; DeVree, Brian T.; Rosenbaum, Daniel M.; Thian, Foon Sun; Kobilka, Tong Sun; Schnapp, Andreas; Konetzki, Ingo; Sunahara, Roger K.; Gellman, Samuel H.; Pautsch, Alexander; Steyaert, Jan; Weis, William I.; Kobilka, Brian K.
- Issue Date
- Jan-2011
- Publisher
- Nature Publishing Group
- Citation
- Nature, v.469, no.7329, pp.175 - 180
- Indexed
- SCIE
SCOPUS
- Journal Title
- Nature
- Volume
- 469
- Number
- 7329
- Start Page
- 175
- End Page
- 180
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/38304
- DOI
- 10.1038/nature09648
- ISSN
- 0028-0836
- 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 beta(2) adrenergic receptor (beta(2)AR) that exhibits G protein-like behaviour, and obtained an agonist-bound, active-state crystal structure of the receptor-nanobody complex. Comparison with the inactive beta(2)AR structure reveals subtle changes in the binding pocket; however, these small changes are associated with an 11 angstrom 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.
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Collections - COLLEGE OF ENGINEERING SCIENCES > DEPARTMENT OF BIONANO ENGINEERING > 1. Journal Articles
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