Details

Autor(en) / Beteiligte

• RASMUSSEN, Soren G. F
• CHOI, Hee-Jung
• SCHNAPP, Andreas
• KONETZKI, Ingo
• SUNAHARA, Roger K
• GELLMAN, Samuel H
• PAUTSCH, Alexander
• STEYAERT, Jan
• WEIS, William I
• KOBILKA, Brian K
• FUNG, Juan Jose
• PARDON, Els
• CASAROSA, Paola
• PIL SEOK CHAE
• DEVREE, Brian T
• ROSENBAUM, Daniel M
• SUN THIAN, Foon
• SUN KOBILKA, Tong

Titel

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

Ist Teil von

• Nature (London), 2011-01, Vol.469 (7329), p.175-180

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2011

Quelle

EBSCOhost Psychology and Behavioral Sciences Collection

Beschreibungen/Notizen

• G protein coupled receptors (GPCRs) exhibit a spectrum of functional behaviors 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 β 2 adrenergic receptor (β 2 AR) that exhibits G protein-like behavior, and obtained an agonist-bound, active-state crystal structure of the receptor-nanobody complex. Comparison with the inactive β 2 AR structure reveals subtle changes in the binding pocket; however, these small changes are associated with an 11Å 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.