Structure of a nanobody-stabilized active state of the ß(2) adrenoceptor.
Nature
; 469(7329): 175-80, 2011 Jan 13.
Article
em En
| MEDLINE
| ID: mdl-21228869
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 ß(2) adrenergic receptor (ß(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 ß(2)AR 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Imunoglobulinas
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Receptores Adrenérgicos beta 2
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Nanoestruturas
/
Agonistas de Receptores Adrenérgicos beta 2
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article